Category Archives: Molecular Medicine

VENTURA, Calif., Nov. 22, 2019 /PRNewswire/ --A California-based pet wellness company has launched a new natural health supplement formulated to boost your pet's immune system and protect dogs and cats against cancer and other life-threatening diseases.

"Cancer is the number-one killer of dogs and cats," explains VetSmart Formulas founder and CEO, Russ Kamalski. "We wanted to create a product that would help pets stay healthy and active for years to come. That's why we've spent the past few years perfecting the formula and making sure it includes active ingredients that have been proven to promote normal cell growth and support long-term health in pets."

The supplement's main ingredients are four medicinal mushrooms from Asia that have been proven to inhibit the growth of cancerous tumors, strengthen the immune system, lower cholesterol levels and blood pressure, and reduce inflammation. The product also includes a patented white turmeric extract that contains active ingredients that have been shown to protect against neurodegenerative diseases, arthritis, cardiovascular risks, and liver damage.

Kamalski says that the powerful combination of natural ingredients is one of the most effective antioxidant supplements for pets and is designed to strengthen the immune system for both young pets as a preventative measure, and for those dogs and cats struggling with diseases such as cancer, it helps the pet's natural immune defenses in an extraordinary way.

"It is the responsibility of the pet owner to do everything possible to minimize the risk of cancer in their pets. That includes a sensible lifestyle with sufficient exercise, weight management, drinking clean water, healthy food intake, and avoiding toxins," says Doctor of Veterinary Medicine Shawn Messonnier, founder of Paws & Claws Animal Hospital in Plano, Texas. "Giving your pets a high-quality antioxidant supplement is highly recommended to further reduce the risk of cancer."

Kamalski, who has decades of experience in the natural health supplement industry, decided to develop this all-natural supplement when his 12-year-old dog, Sienna, developed bone cancer. The doctors gave her just a few months to live but Kamalski exhaustively researched alternative cancer treatments and developed an early prototype of the Critical Immune Defense formula to aid in her treatment and recovery. With the support of Sienna's veterinarian and oncologist, he succeeded in extending Sienna's life by almost two years.

"The oncologists who were treating her were amazed," Kamalski says. "Her tumors basically stopped growing and started to shrink. Not only did the product help slow the cancer growth, her quality of life dramatically improved. They'd never seen anything like it."

Critical Immune Defense is not available in retail stores and can be found at the Pet Wellness Direct Website: http://getvsf.com/cid-press

About VetSmart Formulas:VetSmart Formulas is a line of high-quality pet supplements sold directly to consumers by Pet Wellness Direct, an online pet wellness company founded in 2015. The company's all-natural products are made in the USA in FDA audited labs, have no artificial ingredients or flavors, are wheat-free, and are based on scientifically superior formulas that pet professionals demand. The company's board of advisors includes a professor of biochemistry and molecular medicine and four veterinarians who are passionate about protecting our pets from disease and increasing pet health and longevity.

Related Links:

Russ KamalskiCEOPet Wellness Direct888-212-8400, ext. 802inquiries@petwellnessdirect.com

This release was issued through WebWire. For more information visit http://www.webwire.com.

SOURCE Pet Wellness Direct

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New Immune-Boosting Pet Supplement May Add Years to the Life of Your Pet - PRNewswire

Vyriad, a company in southeastern Minnesota that is designing viruses to selectively kill cancer cells, has signed a major agreement with the biotech drugmaker Regeneron to collaborate on drug therapies to target melanoma and cancers of the lung, liver and uterus.

A Vyriad spokesman said the agreement would lead to a doubling of the 20-person workforce that Vyriad and its sister company, Imanis Life Sciences, share in Rochester. Vyriad is also planning to expand its research and manufacturing space, moving it out of the Mayo Clinic and into a new 25,000-square-foot facility.

Vyriad has a close relationship with Mayo, using intellectual property licensed from the Mayo Clinic and having been co-founded by Mayo researcher Dr. Stephen Russell, who founded the clinics Molecular Medicine Department and built an oncolytic virotherapy program there.

The relationship is a big reason Vyriad remains in Minnesota. Russell said in an interview that Vyriad has heard feedback from private venture-capital firms that have said they would be more likely to invest in Vyriad if the company moved to a traditional biotech hub like Boston or San Francisco. But Vyriads close link with Mayo and the Rochester community is too important for the company to leave town.

The link with Mayo Clinic is enormously valuable to the company. We are built on technology that was developed at Mayo Clinic, and there is a pipeline of related technologies being developed at Mayo. The founding scientists live in Rochester. They work at Mayo Clinic, Russell said. In addition, there is the DMC [Destination Medical Center] effort going on, and there is a definite will in the community to build biotech in Rochester.

Unlike venture-capital firms that were overly concerned about recruiting top executive talent to southeastern Minnesota, Regeneron was more interested in whether the collaboration was scientifically sound, Russell said.

Under the collaboration agreement with Regeneron, the New York-based drugmaker made an equity investment in Vyriads Series B fundraising round. Following a successful closing of a $10 million Series A round in 2017, Vyriads ongoing Series B round has raised $24.4 million toward its goal of $37.8 million, including the Regeneron contribution, according to a filing with the Securities and Exchange Commission.

Regenerons equity investment comes in addition to a cash payment of undisclosed size made to Vyriad as well. The deal gives Regeneron the ability to exclusively license a Vyriad compound called Voyager-V1 and other products developed under the collaboration, while Vyriad will work exclusively with Regeneron to research and develop vesicular stomatitis virus (VSV)-based treatments.

We are thrilled to partner with Regeneron in this far-reaching collaboration to develop novel cancer treatments, Russell said in the company announcement. We are confident that the clinical combination of Voyager-V1 with Libtayo will result in effective anti-cancer activity

Libtayo, developed and commercialized jointly by Regeneron and Sanofi, is a type of human monoclonal antibody known as a PD-1 inhibitor that, when concentrated into a biologic drug, encourages the immune system to release more cancer-killing T cells. Doctors believe Libtayo can be used in combination with Vyriads investigational intravenous drug candidate Voyager-V1, an engineered VSV that attacks specific cancer cells, activates the anti-tumor immune system, and potentially causes further PD-1 inhibition to kill cancer cells.

Correction: A previous version incorrectly reported the size of Vyriads new research and manufacturing facility.

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Rochester cancer-therapy firm to collaborate with drugmaker on melanoma treatment - Minneapolis Star Tribune

Professor Nikolaus Rajewsky is a visionary: He wants to understand exactly what happens in human cells during disease progression, with the goal of being able to recognize and treat the very first cellular changes. "This requires us not only to decipher the activity of the genome in individual cells, but also to track it spatially within an organ," explains the scientific director of the Berlin Institute for Medical Systems Biology (BIMSB) at the Max Delbrck Center for Molecular Medicine (MDC) in Berlin. For example, the spatial arrangement of immune cells in cancer ("microenvironment") is extremely important in order to diagnose the disease accurately and select the optimal therapy. "In general, we lack a systematic approach to molecularly capture and understand the (patho-)physiology of a tissue."

Maps for very different tissue typesRajewsky has now taken a big step towards his goal with a major new study that has been published in the scientific journal Nature. Together with Professor Nir Friedman from the Hebrew University of Jerusalem, Dr. Mor Nitzan from Harvard University in Cambridge, USA, and Dr. Nikos Karaiskos, a project leader from his own research group on "Systems Biology of Gene Regulatory Elements", the scientists have succeeded in using a special algorithm to create a spatial map of gene expression for individual cells in very different tissue types: in the liver and intestinal epithelium of mammals, as well as in embryos of fruit flies and zebrafish, in parts of the cerebellum, and in the kidney. "Sometimes purely theoretical science is enough to publish in a high-ranking science journal - I think this will happen even more frequently in the future. We need to invest a lot more in machine learning and artificial intelligence," says Nikolaus Rajewsky.

"Using these computer-generated maps, we are now able to precisely track whether a specific gene is active or not in the cells of a tissue part," explains Karaiskos, a theoretical physicist and bioinformatician who developed the algorithm together with Mor Nitzan. "This would not have been possible in this form without our model, which we have named 'novoSpaRc.'"

Spatial information was previously lost

It is only in recent years that researchers have been able to determine - on a large scale and with high precision - which information individual cells in an organ or tissue are retrieving from the genome at any given time. This was thanks to new sequencing methods, for example multiplex RNA sequencing, which enables a large number of RNA molecules to be analyzed simultaneously. RNA is produced in the cell when genes become active and proteins are formed from their blueprints. Rajewsky recognized the potential of single-cell sequencing early on, and established it in his laboratory.

"But for this technology to work, the tissue under investigation must first be broken down into individual cells," explains Rajewsky. This process causes valuable information to be lost: for example, the original location in the tissue of the particular cell whose gene activity has been genetically decoded. Rajewsky and Friedmann were therefore looking for a way to use data from single-cell sequencing to develop a mathematical model that could calculate the spatial pattern of gene expression for the entire genome - even in complex tissues.

The teams led by Rajewsky and Dr. Robert Zinzen, who also works at BIMSB, already achieved a first breakthrough two years ago. In the scientific journal Science, they presented a virtual model of a fruit fly embryo. It showed which genes were active in which cells in a spatial resolution that had never before been achieved. This gene mapping was made possible with the help of 84 marker genes: in situ experiments had determined where in the egg-shaped embryo these genes were active at a certain point in time. The researchers confirmed their model worked with further complex in situexperiments on living fruit fly embryos.

A puzzle with tens of thousands of pieces and colors

"In this model, however, we reconstructed the location of each cell individually," said Karaiskos. He was one of the first authors of both the "Science" study and the current "Nature" study. "This was possible because we had to deal with a considerably smaller number of cells and genes. This time, we wanted to know whether we can reconstruct complex tissue when we have hardly any or no previous information. Can we learn a principle about how gene expression is organized and regulated in complex tissues?" The basic assumption for the algorithm was that when cells are neighbors, their gene activity is more or less alike. They retrieve more similar information from their genome than cells that are further apart.

To test this hypothesis, the researchers used existing data. For liver, kidney and intestinal epithelium there was no additional information. The group had been able to collect only a few marker genes by using reconstructed tissue samples. In one case, there were only two marker genes available.

"It was like putting together a massive puzzle with a huge number of different colors - perhaps 10,000 or so," explains Karaiskos, trying to describe the difficult task he was faced with when calculating the model. "If the puzzle is solved correctly, all these colors result in a specific shape or pattern." Each piece of the puzzle represents a single cell of the tissue under investigation, and each color an active gene that was read by an RNA molecule.

The method works regardless of sequencing technique"We now have a method that enables us to create a virtual model of the tissue under investigation on the basis of the data gained from single-cell sequencing in the computer - regardless of which sequencing method was used," says Karaiskos. "Existing information on the spatial location of individual cells can be fed into the model, thus further refining it." With the help of novoSpaRc, it is then possible to determine for each known gene where in the tissue the genetic material is active and being translated into a protein.

Now, Karaiskos and his colleagues at BIMSB are also focusing on using the model to trace back over and even predict certain developmental processes in tissues or entire organisms. However, the scientist admits there may be some specific tissues that are incompatible with the novoSpaRc algorithm. But this could be a welcome challenge, he says: A chance to try his hand at a new puzzle!

Reference: Nitzan, Karaiskos, Friedman and Nikolaus Rajewsky. 2019. Gene expression cartography. DOI: https://doi.org/10.1038/s41586-019-1773-3.

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Calculating the Spatial Pattern of Gene Expression for the Entire Genome - Technology Networks

COURTESY OF ISABEL THOMAS

Professor Gennerich explained that the two heads of dyenin seem to know their relative positions.

On Nov. 7, the Department of Biology Seminar Series hosted Arne Gennerich of the Albert Einstein College of Medicine. Gennerich utilizes single-molecule technology to probe the function and mechanisms of dynein, a motor protein in our cells.

Single-molecule technology allows researchers to hone in on one molecule, rather than observing a population average. By employing it to observe dynein, Gennerich researches how the motor protein can carry a load to different cellular destinations while walking across microtubules, which web across the cell like railways.

Dynein contains two polypeptides that partly form rings, called heads. Extending from these heads are two stalks, like legs. As if wearing suction cups, the leading stalk cyclically binds and detaches from the microtubule, while its partner stalk attaches to the cargo.

Gennerich described the importance of dynein in diverse processes.

If you were to hurt your toe, ask yourself, how many days [would it take to start] to heal? It turns out if transport would rely on effusion, it would take 107 years. But it takes only a few days for molecular motors that [are] able to move along the nerve towards the toe.

Even neurons that migrate to the surface of the brain, chromosomes that are pulled into daughter cells during cell division, and activated T cell receptors that concentrate in the center of cell are driven by cytoplasmic dynein.

If mutations pop up in the gene regulating cytoplasmic dynein, diseases like microcephaly can occur.

When functioning, however, dynein can take thousands of consecutive steps forward while transporting cargo.

This means that the leading motor domain... must stay bound while the trailing motor domain... must know that its in the back [in order to turn] in[to] a weak binding state, said Gennerich. Even though both motor domains are identical, they are always out of phase.

To understand how this motion and transport is done on a molecular scale, Gennerich and his colleagues developed technology that combine single-molecule fluorescence and optical tweezers.

Single-molecule fluorescence relies on tagging the molecule of interest with fluorescent proteins and studying the emission and reabsorption of photons. This emission and reabsorption changes with time as distance changes, allowing researchers to study the internal dynamics of a molecule.

Optical tweezers use laser beams to trap and manipulate a molecule, which can be pulled like taffy to measure the amount of force necessary to disrupt the structure.

Blending these techniques, Gennerichs lab studied how the two heads of dynein, although identical in structure of motor domains, know where they are relative to each other in order to keep out of phase.

Gennerich hypothesized that the rings that comprise the heads of dynein prefer to be stacked.

[However,] based on step size and [further] analysis, we envisioned that they splayed apart, said Gennerich.

This means that within the same molecule, the leading head feels tension tugging it backwards, while the partner head feels tension pulling it forwards.

With that in mind, Gennerichs lab designed an experiment to probe whether the backwards tension that the leading head feels in fact increases the strength of the binding between the leading head and the microtubule it walks along. Conversely, does forward tension pulling the partner head decrease the binding strength of that partner head?

By engineering a dynein with a fluorescent protein in place of a head, Gennerich and his colleagues could measure the binding strength. They found that dynein changes its binding strength in the direction in which it is pulled. After an initial increase in strength as force applied on dynein increases, dynein becomes insensitive to any more increase in force.

In order to intramolecularly communicate, two helices within the stalk slide. This helix sliding must occur in order for dynein to alter its binding affinity. But some key piece was missing what could induce sliding through tension?

Gennerichs lab hypothesized that the buttress, a structure found below the stalk, was involved. He and his colleagues soon discovered that without stalk-buttress interactions, the stalk helices could only occupy a state of minimal binding.

This tells [us] directly that the buttress mediates tension-induced helix sliding. In other words, the buttress and stalk must communicate in order for the helices to regulate their binding affinity, and for dynein to be able to take thousands of consecutive steps forward along microtubules.

Riti Gupta, a seventh-year PhD candidate whose work also centers on single-molecule techniques applied to motor proteins, attended the presentation. She remarked on the precision of his methods in analyzing dynein can be applied to understand where differences between the work of different scientists arise.

I really liked specifically what he said about how tagging the protein at a specific side can affect the results that you have as well as concentration. [By] pinpoint[ing] where those differences come from... [we can decide whether] experimental conditions need to be changed or examined more carefully.

Continued here:
Seminar talk explains the sliding mechanisms of the motor protein, dynein - Johns Hopkins News-Letter

While the rate of death from cancer has been declining since the 1990s, an estimated 9.6 million people died from cancer in 2018, making it the second-leading cause of death worldwide [1]. According to the NCI Cancer Trends Progress Report, in the United States, the incidence and death rates of some cancer types have also been increasing. Together, these facts indicate that despite tremendous recent progress, the research community unfortunately still has a long list of tasks to complete to end global suffering from cancer.

The clinical management of cancer has long been rooted in morphological and histopathological analyses for diagnosis, and the triad of surgery, chemotherapy, and radiation for treatment. However, we are quickly moving towards a pervasive reliance on high resolution, high throughput, molecular marker-based diagnostic as well as precision-targeted therapeutic modalities. The progressive development of the paradigm that defined molecular drivers of cancer has exposed therapeutic vulnerabilities; for example, the BCR-ABL1 gene fusion in chronic myeloid leukemia, KIT mutations in gastrointestinal stromal tumors, ERBB2 amplification in a subset of breast cancers, or EGFR mutations and ALK/ ROS/ RET gene fusions in lung cancers to name a few. Fueled by advances in high-throughput sequencing, it is increasingly practical (and arguably affordable) to systematically pursue Targeted Anticancer Therapies and Precision Medicine in Cancer.

PLOS ONE, together with PLOS Computational Biology, launched a Call for Papers earlier this year to increase understanding of this clinically important area. The scope of this call encompassed four areas: identification and classification of driver genes and somatic alterations; target and drug discovery; mechanisms of drug resistance; and early detection and screening.

Today, we are very happy to announce the launch of the resulting Collection. Featuring an initial set of nearly two dozen papers, with more to be added as they are published, these articles represent diverse facets of ongoing efforts in this area, where general knowledge of cancers serves to inform individual patients care, and at the same time particulars from individual cancer cases contribute to improved resolution of our general knowledge pool.

Somatic aberrations that are critical to the development, growth and progression of cancer are defined as drivers that are typically accompanied by large numbers of incidental aberrations referred to as passengers, acquired in the tumors due to the general chromosomal instability characteristic of advanced cancers. Distinguishing driver aberrations from passengers in individual tumors represents an active area of research that involves development of smarter analytical algorithms, as well as definitive functional characterization of candidate aberrations.

Emilie A. Chapeau et al. developed a conditional inducible transgenic JAK2V617F mouse model that recapitulates aspects of human myeloproliferative neoplasms, including splenomegaly, erythroid expansion and hyperproliferation of bone marrow, with some intriguing differences seen between male and female mice. Importantly, the disease phenotype was reversible when transgene expression was switched off. This work underscores the key role for JAK2V617F in the initiation and maintenance of myeloproliferative neoplasms, and suggests that inhibitors specific to this JAK2 mutation might be efficacious in this disease [2].

Using targeted exon sequencing and array comparative genomic hybridization (CGH), Gayle Pageau Pouliot et al. identified monoallelic mutations in Fanconi-BRCA pathway genes in samples collected from children with T cell acute lymphoblastic leukemia (T-ALL). These mutations appeared to arise in early stages of tumorigenesis, suggesting a potential role for Fanconi-BRCA pathway insufficiency in the initiation of T-ALL. Although PARP inhibitors did not affect viability of isolated T-ALL cells with monoallelic Fanconi-BRCA mutations, these cells were hypersensitive to UV irradiation in vitro or ATR inhibition in vivo, suggesting that ATR inhibitors might have therapeutic value in T-ALL [3].

Three papers in this Collection examine links between genetic alterations and prognosis. Sumadi Lukman Anwar et al. report that LINE-1 hypomethylation in human hepatocellular carcinoma samples correlates with malignant transformation, decreased overall survival and increased tumor size [4]. Investigating HER2-positive breast cancer specimens, Arsalan Amirfallah et al. found that high levels of vacuole membrane protein 1 (VMP1) could potentially contribute to cancer progression and might be a marker of poor prognosis [5]. Finally, in their systematic review and meta-analysis, Chia Ching Lee et al. identified low discordance rates in EGFR mutations between primary lung tumors and distant metastases, although they note some differences depending on metastatic site. Notably, discordance rates appear to be higher in bone metastases compared to central nervous system or lung metastases [6]. These studies provide much-needed leads for the potential development of new diagnostic tests or targeted therapies.

Precision therapy of cancers is premised on the identification of tumor-specific driver aberrations that are necessary for tumor growth and survival. These aberrations represent potential therapeutic targets. While matching therapeutics have been developed for some of the tumor-specific targets, particularly many oncogenic kinases, a large number of defined driver aberrations remain in search of effective therapies. Drug discovery efforts to match defined targets represent a vigorous area of ongoing research with implications for survival and quality of lives of cancer patients worldwide. The development of drugs to treat cancers driven by transcription factors, chromatin modifiers, and epigenetic modulators has proved particularly challenging. On the other hand, recent development of novel immunotherapeutic approaches has spurred research to identify potential targets and matching drug discovery efforts.

This Collection highlights several interesting new strategies to identify potential lead compounds for cancer treatment. Thomas W. Miller et al. describe the development of a biochemical quantitative high-throughput screen for small molecules that disrupt the interaction between CD47 and SIRP. Preclinical studies have shown that disrupting this interaction may provide a new approach for cancer immunotherapy. Small molecular inhibitors that specifically target the interaction between CD47 and SIRP are potentially advantageous over biologics that target CD47, because they might have less on target toxicologic issues and greater tissue penetrance [7].

Work from Gabrielle Choonoo, Aurora S. Blucher et al. examines the feasibility of repurposing existing cancer drugs for new indications. The authors compiled information about somatic mutations and copy-number alterations in over 500 cases of head and neck squamous cell carcinoma (HNSCC) and mapped these data to potential drugs listed in the Cancer Targetome [8]. This approach uncovered pathways that are routinely dysregulated in HNSCC and for which potential anti-cancer therapies are already available, as well as those for which no therapies exist. The work opens new therapeutic avenues in the treatment of this disease and also illuminates which pathways could be prioritized for the development of therapies [9].

Another important approach in extending the clinical utility of existing anti-cancer drugs is to determine whether they are effective in other settings. Indeed, Kirti Kandhwal Chahal et al. have demonstrated that the multi-tyrosine kinase inhibitor nilotinib, which is approved for use in chronic myeloid leukemia, binds the Smoothened receptor and inhibits Hedgehog pathway signaling. Nilotinib decreased viability of hedgehog-dependent medulloblastoma cell lines in vitro and in patient-derived xenografts in vivo, suggesting that nilotinib might be an effective therapy in Hedgehog-dependent cancer [10]. (Check out the authors preprint of this article on bioRxiv.) Darcy Welch, Elliot Kahen et al. took a different approach to identify new tricks for old drugs. By testing two-drug combinations of five established (doxorubicin, cyclophosphamide, vincristine, etoposide, irinotecan) and two experimental chemotherapeutics (the lysine-specific demethylase 1 (LSD1) inhibitor SP2509 and the HDAC inhibitor romidepsin), they found that combining SP2509 with topoisomerase inhibitors or romidepsin synergistically decreased the viability of Ewing sarcoma cell lines in vitro [11].

Two papers in this collection describe potential new therapeutic approaches in cancer. Vagisha Ravi et al. developed a liposome-based delivery mechanism for a small interfering RNA targeting ferritin heavy chain 1 (FTH1) and showed that this increased radiosensitivity and decreased viability in a subpopulation of glioma initiating cells (GICs) [12]. Yongli Li et al. identified 2-pyridinealdehyde hydrazone dithiocarbamate S-propionate podophyllotoxin ester, a podophyllotoxin derivative that inhibits matrix metalloproteinases and Topoisomerase II. Treatment with this compound decreased the migration and invasion of human liver cancer cell lines in vitro, as well as growth of HepG2-derived tumors in mouse xenografts [13].

The success of precision cancer therapy targeting defined somatic aberrations is hampered by an almost inevitable, eventual treatment failure due to the emergence of drug resistance. Resistance often involves new mutations in the therapeutic target itself, or it may result due to activation of alternative pathways. Identification and therapeutic targeting of drug resistant clones represents an ongoing research problem with important practical implications for the clinical management of cancer.

Afatinib is a pan-human epidermal growth factor receptor (HER) inhibitor under investigation as a potential therapeutic option for people with gastric cancer; however, preclinical studies have found that some gastric cancer cell lines are resistant to afatinib treatment. Karolin Ebert et al. identify a potential mechanism behind this lack of response, demonstrating that siRNA-mediated knockdown of the receptor tyrosine kinase MET increases afatinib sensitivity of a gastric cancer cell line containing a MET amplification. As upregulation of MET has been linked to resistance to anti-HER therapies in other cancers, these findings support a role for MET in afatinib resistance in gastric cancer and suggest that combined afatinib and anti-MET therapy might be clinically beneficial for gastric cancer patients [14].

Identifying mechanisms to circumvent drug resistance is critically important to improve response and extend survival, but it is equally important to identify individuals who could be at risk of not responding to anti-cancer therapeutics. Lucas Maahs, Bertha E. Sanchez et al. report progress towards this end, showing that high expression of class III -tubulin in metastatic castration-resistant prostate cancer (CRPC) correlated with decreased overall survival and worse response rate (as measured by changes in prostate-specific antigen (PSA) levels) in CRPC patients who received docetaxel therapy. The development of a biomarker indicating potential treatment resistance to docetaxel could help develop treatment plans with the best chance of success [15].

The converse approach identifying biomarkers that correlate with drug sensitivity could help distinguish subsets of patients who would benefit most from a certain anti-cancer therapy. Kevin Shee et al. mined publicly available datasets to identify genes whose expression correlate with sensitivity and response to chemotherapeutics and found that expression of Schlafen Family Member 11 (SLFN11) correlates with better response to a variety of DNA-damaging chemotherapeutics in several types of solid tumors [16]. Separately, Jason C. Poole et al. validated the use of the Target Selector ctDNA assay, a technology developed by their group that allows the specific amplification of very low frequency mutant alleles in circulating tumor DNA (ctDNA). Testing for EGFR, BRAF and KRAS mutations yielded a very high, >99% analytical sensitivity and specificity with the capability of single mutant copy detection, indicating that accurate molecular disease management over time is possible with this minimally invasive method [17].

Work from Georgios Kaissis, Sebastian Ziegelmayer, Fabian Lohfe et al. uses a machine learning algorithm to differentiate subtypes of pancreatic ductal adenocarcinoma based on 1,606 different radiomic features. Intriguingly, the subtypes identified in their analysis correlated with response to chemotherapeutic regimens and overall survival [18]. An imaging approach taken by Seo Young Kang et al. demonstrates the potential power of fluorodeoxyglucose (FDG) PET/CT scans in determining the response of people with metastatic differentiated thyroid cancer to radioactive iodine treatment [19].

Since cancer growth and development accrues progressive accumulation of somatic aberrations, early detection holds the promise of more effective interventions. Similarly, screening of at risk demographics has been found effective in preventing or better managing cancer care, as exemplified by the significant reduction in cases of cervical cancer after the introduction of the Pap smear as well as human papillomavirus (HPV) testing.

Biomarker development is also critically important for the early detection of cancer and metastatic disease; moreover, biomarkers are being identified that can provide insight into patient prognosis. Several papers in this Collection report interesting findings in the area of biomarker development. A report from Lingyun Xu et al. describes a magneto-nanosensor-based multiplex assay that measures circulating levels of PSA and four proteins associated with prostate cancer. This approach segregates people with prostate cancer from those with benign prostate hyperplasia with high sensitivity and specificity [20].

Two articles provide new insight into markers of disease progression and survival. Vidya Balagopal et al. report the development of a 22-gene hybrid-capture next generation sequencing panel to identify measurable residual disease in patients with acute myeloid leukemia (AML). In their retrospective study, the panel was effective at detecting evidence for residual disease. Importantly, it correctly identified patients who had never relapsed in that no evidence of residual disease was detected in any of these respective samples. Once validated, this approach could potentially be useful in monitoring patients with AML to ensure that recurrence or relapse is identified as soon as possible [21]. Separately, Yoon-Sim Yap et al. use a label-free microfluidic platform to capture circulating tumor cells (CTCs) from people with breast cancer and show that absolute numbers of CTCs predict progression-free survival with higher levels of CTCs correlating with a worse prognosis [22].

Finally, Lucia Suzuki et al. report findings into a potential role for the intestinal stem cell marker olfactomedin 4 (OLFM4) as a biomarker for metastasis in esophageal adenocarcinoma. The authors found that OLFM4 expression was not significantly associated with disease-free or overall survival; however, low OLFM4 expression was detected in poorly differentiated early and advanced-stage esophageal adenocarcinoma and was an independent prognostic variable for lymph node metastasis [23].

This collection of studies encompassing the range of research topics under the banner of targeted anticancer therapies highlights the diversity, complexity and inter-disciplinary nature of research efforts actively contributing to our collective knowledge base with the hope to positively impact the lives of all cancer patients.

We would like to thank all Academic Editors and reviewers for their expert evaluation of the articles in this Collection as well as the authors for their contributions to this field. Special thanks to Senior Editor, Team Manager Emily Chenette for her invaluable help and guidance in publishing this Collection.

Andrew Cherniack

Andrew Cherniack is a group leader in the Cancer Program at the Broad Institute of MIT and Harvard and in the Department of Medical Oncology at the Dana Farber Cancer Institute. He led the Broad Institutes effort to analyze somatic DNA copy number alterations for The Cancer Genome Atlas (TCGA) and is now co-principal investigator of the Broad Institutes copy number Genome Data Analysis Center for the National Cancer Institutes Genomic Data Analysis Network (GDAN). He also leads the oncoming effort to identify new cancer therapeutic targets for the partnership with Bayer. Prior to joining the Broad Institute in 2010, Dr. Cherniack worked in both academia and industry, with a 9-year tenure at the Abbott Bioresearch Center following a similar time period in the Program in Molecular Medicine at UMass Medical School, where he was a postdoctoral researcher and a research assistant professor. Dr. Cherniack holds a Ph.D. in molecular genetics from Ohio State University and a B.A. in biology from the University of Pennsylvania.

Anette Duensing

Anette Duensing is an Assistant Professor of Pathology at the University of Pittsburgh School of Medicine and a Member of the Cancer Therapeutics Program at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center. Dr. Duensings research focuses on bone and soft tissue sarcomas with the goal of identifying novel therapeutic approaches that target the underlying molecular biology of these malignancies. Her special interest and expertise are in gastrointestinal stromal tumors (GISTs), a sarcoma characterized by mutations in the KIT or PDGFRA receptor tyrosine kinases and the first solid tumor entity that was successfully treated with small molecule kinase inhibitors. Dr. Duensing holds an M.D. degree from the University of Hannover School of Medicine, Germany, and was a research scholar of the Dr. Mildred Scheel Stiftung fr Krebsforschung (German Cancer Aid/Deutsche Krebshilfe) at Brigham and Womens Hospital, Harvard Medical School. She is the recipient of an AACR Scholar-in-Training Award (AACR-AstraZeneca), a Young Investigator Award from The Liddy Shriver Sarcoma Initiative, a UPCI Junior Scholar Award, a Jeroen Pit Science Award, a Research Award from the GIST Group Switzerland and was named Hillman Fellow for Innovative Cancer Research. Dr. Duensing is co-founder and leader of the Pittsburgh Sarcoma Research Collaborative (PSaRC), a highly translational, interdisciplinary sarcoma research program. She is also affiliated with the Department of Urology at the University of Heidelberg, Germany. Dr. Duensing is an Academic Editor for PLOS ONE and author of nearly 70 original articles, reviews and book chapters.

Steven G. Gray

Steven Gray graduated from Trinity College Dublin in 1992. He joined the laboratory of Tomas J. Ekstrm at the Karolinska Institute (Sweden) in 1996 and received his PhD in 2000. He moved to the Van Andel Research Institute in Michigan, USA where he continued his studies on the therapeutic potential of histone deacetylase inhibitors in the treatment of cancer. He also spent time as a visiting fellow at Harvard Medical School, Boston working on epigenetic therapies for neurodegenerative disease. Returning to Europe, Dr. Gray spent some time at the German Cancer Research Centre (DKFZ Heidelberg), and subsequently moved to Copenhagen to work for Novo Nordisk as part of the research team of Prof Pierre De Meyts at the Hagedorn Research Institute working on epigenetic mechanisms underpinning diabetes pathogenesis. Dr. Gray is currently a senior clinical scientist at St Jamess Hospital at the Thoracic Oncology Research Group at St. Jamess Hospital. He holds adjunct positions at both Trinity College Dublin (senior clinical lecturer with the Dept. of Clinical Medicine), and at Technical University Dublin (adjunct senior lecturer, School of Biology DIT). Dr. Gray has published over 100 peer-reviewed articles, 15 book chapters and has edited 1 book. Research in Dr Grays laboratory focuses on Receptor Tyrosine Kinases as potential therapeutic targets for the treatment of mesothelioma; epigenetic mechanisms underpinning drug resistance in lung cancer; targeting epigenetic readers, writers and erasers for the treatment of mesothelioma and thoracic malignancy; circulating tumour cells; and non-coding RNA repertoires in mesothelioma and thoracic malignancy.

Sunil Krishnan

Sunil Krishnan is the Director of the Center for Radiation Oncology Research and the John E. and Dorothy J. Harris Professor of Gastrointestinal Cancer in the department of Radiation Oncology at MD Anderson Cancer Center. He received his medical degree from Christian Medical College, Vellore, India and completed a radiation oncology residency at Mayo Clinic, Rochester, Minnesota. In the clinic, he treats patients with hepatobiliary, pancreatic and rectal tumors with radiation therapy. His laboratory has developed new strategies and tools to define the roles and mechanisms of radiation sensitization with gold nanoparticles, chemotherapeutics, biologics and botanicals. Dr. Krishnan serves as the co-chair of the gastrointestinal scientific program committee of ASTRO, co-chair of the gastrointestinal translational research program of RTOG, consultant to the IAEA for rectal and liver cancers, chair of the NCI pancreatic cancer radiotherapy working group, and Fellow of the American College of Physicians. He has co-authored over 200 peer-reviewed scientific publications, co-authored 17 book chapters, and co-edited 3 books.

Chandan Kumar-Sinha

Chandan Kumar-Sinha is a Research Associate Scientist in the Department of Pathology at the University of Michigan. He obtained Masters in Biotechnology from Madurai Kamraj University, and PhD in Plant Molecular Biology from Indian Institute of Science. He completed a Postdoctoral Fellowship at the Department of Pathology, University of Michigan, where he worked on genomic profiling of cancers. Thereafter, he joined the Advanced Center for Treatment, Research and Education in Cancer in India as a faculty member. After establishing a cancer genomics group there, he moved back to the University of Michigan to pursue translational cancer research. Dr. Kumar-Sinhas current research involves integrative clinical sequencing using high-throughput genome and transcriptome analyses to inform precision oncology. He has authored over 50 peer-reviewed publications, two book chapters, and is named co-inventor on a patent on prostate cancer biomarkers.

Gayle E. Woloschak

Gayle Woloschak is Professor of Radiation Oncology, Radiology, and Cell and Molecular Biology in the Feinberg School of Medicine, Northwestern University. Dr. Woloschak received her Ph.D. in Medical Sciences from the University of Toledo (Medical College of Ohio). She did her postdoctoral training at the Mayo Clinic, and then moved to Argonne National Laboratory until 2001. Her scientific interests are predominantly in the areas of molecular biology, radiation biology, and nanotechnology studies, and she has authored over 200 papers. She is a member of the National Council on Radiation Protection, the International Commission on Radiation Protection and numerous other committees and also serves on the US delegation to the United National Scientific Committee on the Effects of Atomic Radiation.

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Introducing the Targeted Anticancer Therapies and Precision Medicine in Cancer Collection - PLoS Blogs

For anyone not familiar with ARK Invest, they have a suite of ETF strategies dedicated to helping investors hone in on disruptive innovations and technologies with the potential to affect the global economy.

We focus solely on disruptive innovation. We try to identify the company in the public market that are the leaders, enablers and beneficiaries of technology and innovation the companies that are trying to change how the world works in the future with the three to five year investment horizon. So, we take that research and we offer thematic strategies to our investors, Sebastian Benkert, CMO, ARK Invest, said at the 2019 Charles Schwab IMPACT conference.

For example, ARK Invests flagship ARK Innovation Fund (NYSEArca: ARKK) seeks to invest in the cornerstone companies taken from healthcare, technology and industrial sectors that focus on investing in disruptive innovation. Such companies may include ones that benefit from big data, cloud computing, cryptocurrencies, the sharing economy, genomic sequencing, molecular medicine, agricultural biology, 3D printing, energy storage, and autonomous vehicles.

The actively managed fund includes companies that merge healthcare with technology and capitalize on the revolution in genomic sequencing. These companies try to better understand how biological information is collected, processed, and applied by reducing guesswork and enhancing precision; restructuring health care, agriculture, pharmaceuticals and enhancing our quality of life.

The technology component focuses more in the next generation of internet names. These tech companies benefit from the shifting bases of technology infrastructure to the cloud, enabling mobile, new and local services, such as companies that rely on or benefit from the increased use of shared technology, infrastructure and services, internet-based products and services, new payment methods, big data, the internet of things, and social distribution and media.

Lastly, the industrial exposure covers a so-called new industrial revolution or advances in autonomous vehicles, robotics, 3D printing, and energy storage technology that are enhancing productivity, reducing costs, and transforming the manufacturing landscape.

Additionally, investors can look to theARK Industrial Innovation ETF (NYSEArca: ARKQ), ARK Web x.0 ETF (NYSEArca: ARKW) and ARK Genomic Revolution Multi-Sector Fund (NYSEArca: ARKG) to target the three innovative segments separately. The ARK Industrial Innovation ETF captures the converging industrial and technology sectors, capitalizing from autonomous vehicles, robotics, 3D printing, and energy storage technologies. The ARK Web x.0 ETF targets next-gen internet innovations like artificial intelligence, cloud computing, cryptocurrencies, and blockchain technology. Lastly, the ARK Genomic Revolution Multi-Sector ETF tracks the convergence of tech and health care.

For more ETF-related commentary from Tom Lydon and other industry experts, visit ourvideo category.

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ARK Invest ETFs Track Disruptive Companies Changing the World - ETF Trends

The American Heart Association has awarded its Research Achievement Award, recognizing a lifetime of extraordinary contributions to cardiovascular research, to Peter Libby, M.D., FAHA, Mallinckrodt Professor of Medicine at Harvard Medical School and a cardiovascular specialist at Brigham and Womens Hospital (BWH) in Boston.

Dr. Libbys pioneering work unraveling the role of inflammation in cardiovascular disease has been nothing short of paradigm changing. His career-long quest to understand how inflammation contributes to atherogenesis substantially deepened our understanding of heart disease, and his ability to translate his findings into the clinic has led to the development of novel new treatment strategies, said American Heart Association President Robert A. Harrington, M.D., FAHA, who presented the award.

Dr. Libbys independent research career included numerous first discoveries in the pathogenesis of atherosclerosis, including some of the mechanisms that lead to heart attack and stroke, said Dr. Harrington.

The award was presented today at the American Heart Associations Scientific Sessions 2019 in Philadelphia. The Associations Scientific Sessions is an annual, premier global exchange of the latest advances in cardiovascular science for researchers and clinicians.

Dr. Libby instigated and helped to lead the first large-scale, randomized clinical trial establishing inflammation as a therapeutic target in cardiovascular disease. His laboratory has focused on investigating the molecular and cellular mechanisms of atherosclerosis, and he continues to lead investigations that will add to our understanding of risk factors for atherosclerotic events and heart failure, among other important research questions, the award notes.

Inflammation was not considered a critically important contributor to atherogenesis prior to Dr. Libbys investigations. Indeed, the field focused largely on lipid metabolism and proliferation of smooth muscle cells when Dr. Libby began his independent research career, noted Jonathan D. Smith, professor of molecular medicine at the Cleveland Clinic, in a letter nominating Dr. Libby for the Research Achievement Award.

Over 30 years of research, Dr. Libbys discoveries included the finding that vascular wall cells can produce, as well as respond to, pro-inflammatory cytokines (especially Interleukin-1) small proteins that are important in cell signaling.

This discovery, initially met with considerable skepticism, laid the foundation for the recognition of novel paracrine and autocrine inflammatory cytokine signaling pathways in arterial disease, a mechanism now widely validated, Smith concluded.

Dr. Libby is a longtime American Heart Association volunteer. He is also a consulting physician at the Dana-Farber Cancer Institute. He served as Chief of Cardiovascular Medicine at BWH from 1998-2014 after heading its Vascular Medicine and Atherosclerosis Unit from 1990-1997. Prior to joining BWH, Dr. Libby was at Tufts New England Medical Center in Boston.

Dr. Libby earned his medical degree at the University of California, San Diego, and completed his training in internal medicine and cardiology at the Peter Bent Brigham Hospital (now Brigham and Womens Hospital). He also holds an honorary Master of Arts degree from Harvard University, and honorary doctorates from the Universit de Lille, France, and Universit Laval in Qubec. He has received numerous awards and recognitions for his research accomplishments, including the Basic Research Prize of the American Heart Association (2011), the Anitschkow Prize in Atherosclerosis Research of the European Atherosclerosis Society (2013), the Special Award of the Heart Failure Association of the European Society of Cardiology (2014) and the Ernst Jung Gold Medal for Medicine( 2016.) He has received a number of other awards including several lifetime achievement awards from various organizations.

Continued here:
Dr. Peter Libby, who discovered role of inflammation in cardiovascular disease, wins AHA's Research Achievement Award Cardiology2.0 - Cardiology2.0

BOSTON--(BUSINESS WIRE)--Novo Ventures and the Broad Institute of MIT and Harvard announced today the launch of the Novo Broad Greenhouse, a joint initiative to discover and propel transformative new therapies from academic science into the clinic.

To drive the development of the next generation of molecular medicines, the Novo Broad Greenhouse unites three core ingredients: deep basic science expertise from academia, world class drug-discovery capabilities from the Broad Institutes Center for the Development of Therapeutics (CDoT), and a sustainable funding base and therapeutics development expertise from Novo Holdings.

The Novo Broad Greenhouse seeks to accelerate drug discovery projects led by members of the Broad Institute community, spanning institute faculty and professional scientists, including Broad-affiliated faculty at MIT, Harvard, and Harvard-affiliated hospitals.

Novo Holdings, through its US subsidiary, has committed up to $25 million over a five-year period to fund seed-stage drug discovery projects at Broad, spanning a wide range of indications and therapeutic modalities. Seed projects may include efforts to validate new drug targets, to assess how druggable certain proteins or genes are, or to develop new assays to assess the potential of drug candidates.

As projects progress beyond the seed phase, additional, separate funding is envisioned to fund the sprout phase of continued progress towards a clinical candidate, and ultimately the bloom phase -- graduation from the Greenhouse towards definitive clinical testing in patients, supported either by a new biotech company or by a strategic partner.

Novo Holdings investment approach and long-term view allow us to play a sustained role across all stages of drug development, from the earliest discoveries through to pivotal clinical testing, said Thomas Dyrberg, Managing Partner at Novo Holdings. We are thrilled to actively engage with the Boston academic research community in partnership with the Broad and believe this effort can help to catalyze the translation of exciting discoveries into new drug candidates.

The pace at which we can now discover the biological mechanisms and root causes of disease is staggering, said Todd Golub, Chief Scientific Officer of the Broad Institute and a member of the Greenhouses Joint Steering Committee. But in so many cases, these discoveries aren't yet making it past the lab. The Greenhouse gives us a new opportunity to collaborate across boundaries, combining our expertise with our partners to transform our knowledge into the therapies that will benefit patients.

Faculty and professional scientists at CDoT work closely together to translate curiosity-driven academic research into drug discovery projects. In its structure, partnerships, and capabilities, CDoT functions like a pharma or biotech. Most of the centers leadership comes from industry and has extensive drug discovery experience. CDoTs pipeline of projects incorporates multiple therapeutic areas, including cancer, cardiovascular, psychiatric diseases, and immunoregulation. Project stages span the drug discovery process from target validation to lead optimization.

The Novo Broad Greenhouse is one of several early-stage initiatives within Novo Holdings and exemplifies Novo Holdings interest to fund breakthrough science into new medicines. Novo Ventures is one of several investment teams employed by Novo affiliates that supports the investment activities of Novo Holdings, one of the worlds largest life science focused investment companies. Novo Ventures aims to facilitate the investment of approximately $500 million annually in private and public life science opportunities in the US, Europe, and Asia. Given Novo Holdings evergreen funding structure, multiple investment strategies, and global reach, Novo Holdings is uniquely positioned to invest in and support life science companies from inception through commercialization.

About Novo Holdings A/S and Novo VenturesNovo Holdings A/S is a private limited liability company wholly owned by the Novo Nordisk Foundation. It is the holding company of the Novo Group, comprising Novo Nordisk A/S and Novozymes A/S, and is responsible for managing the Foundations assets.

Novo Holdings is recognized as a world-leading life science investor with a focus on creating long-term value. As a life sciences investor, Novo Holdings provides seed and venture capital to development-stage companies and takes significant ownership positions in growth and well-established companies. Novo Holdings also manages a broad portfolio of diversified financial assets.

For more information: http://www.novoholdings.dk/

Novo Ventures is a global team of investment professionals employed by Novo affiliates that supports Novo Holdings investments in private, public, and structured product opportunities in the life sciences industry.

For more information: https://www.novoholdings.dk/investments/ventures/

About Broad Institute of MIT and HarvardThe Broad Institute of MIT and Harvard was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods, and data openly to the entire scientific community.

Founded by MIT, Harvard, Harvard-affiliated hospitals, and the visionary Los Angeles philanthropists Eli and Edythe L. Broad, the Broad Institute includes faculty, professional staff, and students from throughout the MIT and Harvard biomedical research communities and beyond, with collaborations spanning over a hundred private and public institutions in more than 40 countries worldwide.

The Center for the Development of Therapeutics (CDoT) is an organization of professional drug discovery scientists whose mission is to translate the biological insights developed at the Broad into therapeutics. CDoT is deeply embedded within the Broad Institute, but in its structure, capabilities, and leadership experience, CDoT closely resembles the drug discovery group of a pharma/biotech.

For more information: https://www.broadinstitute.org

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Novo Ventures and Broad Institute of MIT and Harvard Launch Drug Discovery Greenhouse to Drive Creation of Innovative New Therapies - Business Wire

Dr. Charles Sawyers work over a 34-year career not only led to the development of the blockbuster drug Gleevec for chronic myelogenous leukemia, but to a better understanding of a concept thats now fundamental to oncology that cancers can overcome powerful drugs to develop resistance. And in a rare example, Sawyers role in creating the prostate cancer drug Xtandi was not born within industry, but from within the halls of academia.

And for those milestones, Sawyers, a Howard Hughes Medical Institute investigator and chair of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center, was just named the first-ever winner of the STAT Biomedical Innovation Award. The award is presented to a top researcher in biomedicine whose work has helped to define their field and, in the process, helped patients. He will accept the honor at the inaugural STAT Summit on Thursday in Cambridge, Mass.

Sawyers wasnt always interested in medicine, though both his parents were physicians, nor did he originally have an eye toward cancer treatments. Still, he did make his way to medical school at Johns Hopkins. He vividly recalled how a lecture on the structure of hemoglobin in the context of sickle cell disease helped him gain an appreciation for how detailed knowledge of a disease and its underpinnings which is what his current field of precision medicine celebrates could yield clues for how to solve therapeutic challenges. It was unbelievably cool, he said.

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And it was the drama of taking care of patients with chronic myelogenous leukemia and curiosity about why certain treatments worked well against the disease that led Sawyers to wonder more about new options. But ultimately, he wanted in on the action. The genetic abnormality that is symptomatic of CML was cloned around the time he was finishing his medical training, and remembered thinking, God, I want to be in the middle of this, he said.

STAT spoke with Sawyers about some of the highlights of his career and broader issues he sees in science. This interview has been condensed and lightly edited.

We hear a lot about how discoveries are often curiosity-driven is that what led to Gleevec?

For me, it was curiosity about why you get leukemia, [and] how does this translocation cause leukemia once it was found.

It was in the early 90s. I was at the University of California, Los Angeles, and had my own lab. BCR-ABL [which is a mutation found in almost all CML patients] is in the cytoplasm of cells and a monoclonal antibody approach [which others were trying] was not even on the table. Youd have to use a small molecule. And the challenge was to make a drug that would be safe.

But that argument had kept a lot of people from doing a deep dive [into CML]. Kind of out of the blue, this group had this small [enzyme inhibitor] program for two or three main targets. One of these seemed to also inhibit [BCR-ABL enzymes] and that became Gleevec. We didnt understand why at the time.

How did you realize Gleevec was going to be a cancer drug?

Seeing patients blood counts come down [as part of a Phase 1 trial] was incredibly gratifying, but we could do that with oral chemotherapy. The dose at which we start to see their blood counts drop matched exactly with lab studies we were doing on their blood cells. The scientist part of me was excited because we were doing exactly what we predicted.

The real amazing result was several months later when we did a bone marrow test to see if the BCR-ABL clone is shrinking in the tumor. I was taking care of a patient whose bone marrow test at six months after taking Gleevec showed zero [of the incriminating chromosome]. I was in my office on a Saturday morning, and this fax comes in, and Im like, Holy cow! I cant get a hold of anybody else in the trial, and so I just called the patient!

But that wasnt the end of the Gleevec story. What happened next?

What later happened is that patients can develop resistance and very quickly. And we figured out the reason. We found resistance in the regions of BCR-ABL where the drug was binding, but it didnt interfere with the [enzyme] activity, so it could still cause leukemia.

That led to all this amazing work and second-generation versions of the drug. That experience told me that if you have a cancer that responds well to a drug but then develops resistance, you need to absolutely understand the molecular basis of resistance with great precision and then you can overcome.

How was the Xtandi experience different than the Gleevec story?

We realized after Gleevec that we needed to go after the androgen receptor [in prostate cancer] in a more aggressive way. But companies we approached were moving away to focus on [work with enzymes].

Thankfully, I had a chemistry partner at UCLA named Mike Jung, who got interested in helping us with this. The big difference is that we found Xtandi in our labs at UCLA with chemistry screening and measuring biological activity. The clinical development I had nothing to do with.

What were the lessons you learned from both those drug discovery processes?

Youve got to know the disease and really have a molecular understanding of the disease and the drug target and how the tumor corresponds to the drug target. Its really about precision science.

The other is persistence and passion. Theres lots of reasons that you could talk yourself out of why its not going to work. Obviously, if its not working, you dont continue.

Stepping back, what has been the most surprising thing in oncology?

I think the benefit from immuno-oncology has been greater than expected. The fact that tumors that have complex genetic alterations can have a dependency on a single driver, to me, is amazing. So, this idea to me that there is a house of cards, and theres a card at the bottom that causes the whole house to collapse that, to me, is probably one of the most unexpected and fundamental insights from this work.

Anything youre disappointed by anything you thought wed have figured out by now?

Were going way too slowly with figuring out combination therapies. I think there are way more excuses, and I find that disappointing. Theres a lot of business development issues because the therapies for combinations are often at different companies. Companies often make their own drugs or buy out other companies [and that slows things down].

A second issue is that its a given that theres going to be more toxicity when you give more than a single agent. Weve shot ourselves in the foot a little bit by adopting this a once-a-day-therapy as the only kind of therapy we put forth for clinical development. Were not willing to accept the old chemotherapy mindset where we give four or five drugs at once, and cause incredibly toxicity for three- to six-month period and then stop treatment. I think we should readdress those kinds of concepts, again, with targeted therapy.

Cancer drugs are among the most expensive, and since you have experience developing them, is that something on your radar?

Its not on the radar on the discovery and development side. One thing I think about and try to project to my trainees is that were problem-solvers and we want to find solutions that can help patients. We think about the cause of whatever were trying to solve, the underlying science, and how we get to do something feasible therapeutically. Question of cost of the drug doesnt really enter into the discussion at all.

But the issue of price is in the zeitgeist and I serve as a director at Novartis (NVS), so Im very aware of [drug pricing] from the company perspective and as a human being who cares about patients having access to drugs it concerns me deeply.

What do you see as big challenges facing science as a whole and the future of the trainees in your lab?

Im optimistic about the ability to solve some of these important medical problems within and outside cancer. I think the science is so compelling that the investment as a country weve made in basic science over 30-plus years has really laid the foundation to make an impact. What I find distressing one is, with our current administration in the White House and this anti-science attitude. Fortunately, budgets have been maintained despite threats to cut them, but they certainly havent grown in any significant way. And I think were losing opportunities to further expand our expertise as a country in leading the way in biomedical research.

As far as the trainees, I feel like sometimes I have to be a cheerleader because the payline for grants are terrible. But theres just nothing like this as a career. Its the joy of trying to solve a complicated problem, but the impact of that is enormously gratifying if patients benefit.

Now were seeing more attention to some of the other issues that influence science, like implicit bias and a diverse workforce. How have you seen them change over the course of your career and how are you thinking about them now?

The conversations about this in any sector of work were almost nonexistent 30 years ago or so.

My lab? Racially [its] not diverse. [In terms of] gender, theres lots of diversity. Among early-career researchers, gender diversity is rich, but later on [there are fewer women because] its the usual things, like childbearing, [that causes them to leave].

I play some role in helping shape that. The lack of diversity, though, is very concerning to me, with African Americans in particular. Its very difficult to convince young minorities to take this delayed gratification approach, where you really dont get your first full-time job until youre in your 30s, and you may not get your first [major research] grant until youre in your mid-40s. Thats not a great advertisement for someone who doesnt have a lot of great role models [in the field] to begin with. Its kind of a Catch-22: We dont have enough diversity in our senior faculty to inspire younger minorities to come into this career path.

Its a gradual process, unfortunately [to change these things].

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Cancer researcher named first STAT Biomedical Innovation Award winner - STAT

This Global Fluoroscopy & C Arms Market byData Bridge Market Researchbrings all the figures needed to corner the Global fluoroscopy and C-arms market by showing all the recent developments, product launches, joint ventures, mergers and accusations done by the key players and brands that are making a mark in the market. Besides it also pinpoints the market drivers and restraints with the help of SWOT analysis.

Global fluoroscopy and C Arms marketis expected to reach at a CAGR of 4.3% in the forecast period of 2019 to 2026.

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Some of the prominent participants operating in this market are GE Healthcare, Koninklijke Philips N.V., Siemens AG, Canon Medical Systems Corporation, Shimadzu Corporation, Carestream Health, EcoRay, Eurocolumbus s.r.l., GEMSS Co., Ltd., Hitachi, Ltd., Hologic Inc., INTERMEDICAL S.r.l., ITALYRAY, PAUSCH Medical GmbH, Varex Imaging Corporation, Whale Imaging, and Ziehm Imaging GmbH among others.

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GE Healthcare founded in 1918, headquarters in New York, U.S., and focuses towards the manufacturing and developer of medical imaging, digital solutions, patient monitoring and diagnostics, drug discovery, biopharmaceutical manufacturing technologies and performance improvement solutions.

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The company has its presence in U.S, Europe, Asia, Americas, Middle East and Africa.

Koninklijke Philips N.V.:

Koninklijke Philips N.V., founded in 1891 and based in Amsterdam, Netherlands. The company focuses on improving peoples health and enabling better outcomes across the health continuum from healthy living and prevention to diagnosis, treatment and home care.

The company has its presence in Netherland, United states, China, Germany, Japan, France, India and Others.

Siemens AG:

Siemens AG, founded in 1896 and based in Munich, Germany. The company provides manufacturing, distributing and services of medical devices and pharma Services. Company is engaged in providing precision medicines, transforming care delivery, innovative technology in area of diagnostics, molecular medicine and many others. The company has its presence in Europe, C.I.S., Africa, Middle East, Americas , Asia, Australia.

Market Developments:

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Data Bridge Market Researchset forth itself as an unconventional and neoteric Market research and consulting firm with unparalleled level of resilience and integrated approaches. We are determined to unearth the best market opportunities and foster efficient information for your business to thrive in the market. Data Bridge endeavors to provide appropriate solutions to the complex business challenges and initiates an effortless decision-making process.

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Fluoroscopy and C-arm Market 2019-2026 with Top Leading Players are EMD Medical Technologies, GE Healthcare, Lepu Medical Technology - Eastlake Times