Hatim Husain, MD, associate professor in the Department of Medicine at UC San Diego, discuses must-haves for successful biomarker testing in lung cancerin particular, nonsmall cell lung cancer (NSCLC)and how the field is adapting to the targeted treatment needs of its patients.

In this interview from the Quality Cancer Care Alliance Summer 2022 National Leadership Summit, Hatim Husain, MD, associate professor in the Department of Medicine at UC San Diego, discuses must-haves for successful biomarker testing in lung cancerin particular, nonsmall cell lung cancer (NSCLC)and how this field of clinical research is adapting to the targeted treatment needs of its patients.

Transcript

How do we improve biomarker testing in lung cancer?

Biomarker testing in lung cancer is truly a cornerstone for treatment selection in patients who have nonsmall cell lung cancer. Improving it really relies on a few principles. One is understanding the importance. Second is getting access to technologies that can obtain the results quickly and reliably. And third is waiting for the test results, when feasible, to inform the treatment decision.

The technologies have really expanded to include both tissue comprehensive testing, as well as plasma-, or blood-based, comprehensive testing. And there are important considerations around time to a test result, as well as comprehensiveness, that is important across each of those strategies. So its really important that we have these results early and up front, as now the number of targetable mutations within genes of interest are really expanding over time.

How has biomarker testing in lung cancer evolved over the last few years?

Over the last several years, theres been additions to our armamentarium of agents that can really target specific mutations that previously were not possible. These include some atypical EGFR mutations, such as the EGFR Exon 20 insertion, KRAS G12C, which is a different mutationwhich previously also had not had precision-oriented therapeutic strategiesas well as other genes, including MET and HER2, which also are on the horizon.

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SUZHOU, China, Aug. 29, 2022 /PRNewswire/ -- On August 20, 2022, Porton Advanced Solutions (hereinafter referred to as "Porton Advanced") and Kun Tuo Medical Research and Development (Beijing) Co., Ltd. (hereinafter referred to as "Kun Tuo") established a strategic partnership in gene and cell therapy R&D, manufacturing and clinical services to accelerate the development and industrialization of innovative drugs.

Through this strategic cooperation, Porton Advanced and Kun Tuo will fully leverage their strengths, client resources and professional team capabilities to deepen cooperation in gene and cell therapy R&D, manufacturing and clinical research, providing one-stop CDMO and clinical research services for innovative drug companies and cooperating to establish a high-quality gene and cell therapy industry ecosystem.

Focusing on gene and cell therapy, Porton Advanced has built CDMO platforms for plasmids, cell therapy, gene therapy, oncolytic virus, nucleic acid therapy and microbial vector based gene therapy .In the process of gene and cell therapy drug development, Porton Advanced can provide CDMO services such as IND-CMC pharmacological research and clinical sample GMP production. Up to now, the cell therapy CDMO platform houses more than 22 cell therapy IND-CMC projects, covering various cell types such as CAR-T, UCAR-T, TCR-T, TIL, CAR-MSC, CAR-NK, NK and RBC.

As a clinical research organization (CRO) specially established by IQVIA for the Chinese market, Kun Tuo inherits its refined quality management system and standards, coupled with abundant clinical resources, offering high quality CRO services throughout IND to NDA. Since its establishment in 2011, Kun Tuo has provided over 1,000 clinical study services for multiple renowned pharmaceutical companies at home and abroad.

Dr. Wang Yangzhou, CEO of Porton Advanced, said, "We are very pleased to announce that we entered into a strategic partnership with Kun Tuo. Porton Advanced focuses on the field of gene and cell therapy and is committed to establishing a global, end-to-end CDMO service platform, while Kun Tuo delves into clinical research services and has very rich clinical resources as well as a highly professional clinical research & reporting team with strict quality standards. Through our in-depth cooperation and integration of resources and advantages, both parties will help to promote the construction of the gene and cell therapy industry ecosystem and empower more new drugs to scale new level based on an integrated drug service platform, thereby allowing enabling public's early access to good medicines."

Wang Ling, General Manager of Kun Tuo, said, "Cell and gene therapy is a new generation of breakthrough therapies after small molecule and large molecule targeted therapies, and it is also one of the most promising sectors of biopharmaceuticals at present. As a full-service CRO focusing on local clinical trials in China, Kun Tuo has built a dedicated team to conduct clinical trials of cell therapy-related products since 2018, and has been taking the lead in the field of cell and gene therapy. We also provide services from clinical development to commercialization strategy research for our clients with the commercialization team of our group company IQVIA, so that the products can serve patients faster and better. Porton Advanced is a well-known CDMO company d with professional and rich experience in drug development and manufacturing in the industry We hope that by joining hands with Porton Advanced, we can combine the expertise and strengths of both sides to provide domestic biopharmaceutical companies with a one-stop solution from drug R&D, clinical trials to commercialization."

About Porton Advanced SolutionsEstablished in Suzhou Industrial Park in December 2018, by its parent company Porton Pharma Solutions Ltd. (Stock Code: 300363), Porton Advanced has built a CDMO platform integrating plasmid, cell therapy, gene therapy, oncolytic virus, nucleic acid therapy and microbial vectors used for gene therapy (MVGTs), providing end-to-end services from cell banking, process development and analytical development, cGMP production to final Fill and Finish , investigator-initiated clinical trials (IIT), investigational new drugs (IND), clinical trials to commercial production. Porton Advanced is dedicated to support sponsors advance their GCT drug development and market launches.

Porton Advanced focuses solely on gene and cell therapy services. Built on the professional experience of its cohort of world-class professionals, as well as on the successes of its parent company, Porton Advanced insists on "Customer First" and the tenet of "Compliance, Expertise, Focus, Open Collaboration". With its key focus on protecting IP for its sponsors, through its comprehensive project management and quality systems, Porton Advanced strives to bring gene and cell therapy products to the clinic and the market through its quality CDMO services, and help bring the best medicine to the public sooner.

About KunTuoKunTuo, as a full-service Contract Research Organization (CRO) specially set up in China by IQVIA (a wholly owned subsidiary of IQVIA) and with a team of nearly 1000 employees, is dedicated to provide high-quality and reliable clinical research services for Pharmaceutical and Medical Device & Diagnostic (MDD) enterprises. Since its establishment in 2011, Kuntuo has provided more than 1000 clinical research services for many well-known pharmaceutical and device companies in China and abroad and now has accumulated rich clinical resources, including more than 10,000 departments' enrollment data and nearly 500 institutions'/departments' process information. Kuntuo inherits IQVIA's sound quality management system and quality standards, and provides biomedical enterprises with higher quality and more responsive service model from IND to NDA through the application and optimization of IQVIA's global operation experience and expertise.

SOURCE Porton Advanced Solutions

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Porton Advanced and Kun Tuo Announce Strategic Partnership to Deepen Gene and Cell Therapy CDMO and Clinical Research Services - PR Newswire

Experiments from the UNC School of Medicine lab of Nobel Prize-winning scientist Aziz Sancar, MD, PhD, show how a common molecular tool for DNA labeling also has anticancer properties worthy of further investigation, especially for brain cancers.

CHAPEL HILL, NC Scientists at the UNC School of Medicine have made the surprising discovery that a molecule called EdU, which is commonly used in laboratory experiments to label DNA, is in fact recognized by human cells as DNA damage, triggering a runaway process of DNA repair that is eventually fatal to affected cells, including cancer cells.

The discovery, published in the Proceedings of the National Academy of Sciences, points to the possibility of using EdU as the basis for a cancer treatment, given its toxicity and its selectivity for cells that divide fast.

The unexpected properties of EdU suggest it would be worthwhile to conduct further studies of its potential, particularly against brain cancers, said study senior author Aziz Sancar, MD, PhD, the Sarah Graham Kenan Professor of Biochemistry and Biophysics at the UNC School of Medicine and member of the UNC Lineberger Comprehensive Cancer Center. We want to stress that this is a basic but important scientific discovery. The scientific community has much work ahead to figure out if EdU could actually become a weapon against cancer.

EdU (5-ethynyl-2-deoxyuridine) is essentially a popular scientific tool first synthesized in 2008 as an analog, or chemical mimic, of the DNA building block thymidine which represents the letter T in the DNA code of adenine (A), cytosine (C), guanine (G) and thymine (T). Scientists add EdU to cells in lab experiments to replace the thymidine in DNA. Unlike other thymidine analogs, it has a convenient chemical handle to which fluorescent probe molecules will bond tightly. It thus can be used relatively easily and efficiently to label and track DNA, for example in studies of the DNA replication process during cell division.

Since 2008, scientists have used EdU as a tool in this way, as published in thousands of studies. Sancar, who won the 2015 Nobel Prize for Chemistry for his seminal work on DNA repair, is one such scientist. When his lab began using EdU, his team unexpectedly observed that EdU-labeled DNA triggered a DNA repair response even when it wasnt exposed to DNA-damaging agents, such as ultraviolet light.

That was quite a shock, Sancar said. So we decided to explore it further.

Following up on the strange observation, the team discovered that EdU, for reasons that are still unclear, alters DNA in a way that provokes a repair response called nucleotide excision repair. This process involves the removal of a short stretch of damaged DNA and re-synthesis of a replacement strand. This is the mechanism that repairs most damage from ultraviolet light, cigarette smoke, and DNA-altering chemo drugs. The researchers mapped EdU-induced excision repair at high resolution and found that it occurs across the genome, and it apparently occurs again and again, since each new repair strand includes EdU and thus provokes the repair response anew.

It had been known that EdU is moderately toxic to cells, though the mechanism of its toxicity had been a mystery. The teams findings strongly suggest that EdU kills cells by inducing a runaway process of futile excision repair, which ultimately leads the cell to terminate itself through a programmed cell-death process called apoptosis.

That discovery was interesting in its own right, Sancar said, because it suggested that researchers using EdU to label DNA need to take into account its triggering of runaway excision repair.

As we speak, hundreds and maybe thousands of researchers use EdU to study DNA replication and cell proliferation in lab experiments without knowing that human cells detect it as DNA damage, Sancar said.

Sancar and colleagues also realized that EdUs properties might make it the basis for an effective brain cancer drug because EdU becomes incorporated into DNA only in cells that are actively dividing, whereas, in the brain, most healthy cells are non-dividing. Thus, in principle, EdU could kill fast-dividing cancerous brain cells while sparing non-dividing, healthy brain cells.

Sancar and his team hope to pursue follow-up collaborations with other researchers to investigate EdUs properties as an anticancer agent.

Prior studies have already found evidence that EdU kills cancer cells, including brain cancer cells, but strangely, no one has ever followed up on those results, Sancar said.

Nucleotide excision repair removes thymidine analog 5-ethynyl-2-deoxyuridine from the mammalian genome was co-authored by Li Wang, Xuemei Cao, Yanyan Yang, Cansu Kose, Hiroaki Kawara, Laura Lindsey-Boltz, Christopher Selby, and Aziz Sancar. Funding was provided by the National Institutes of Health (GM118102, ES02755).

Media contact: Mark Derewicz, UNC School of Medicine, 919-923-0959

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Scientists Discover Surprise Anticancer Properties of Common Lab Molecule | Newsroom - UNC Health and UNC School of Medicine

There are many diagnostic, prognostic, and treatment challenges in managing patients with chronic obstructive pulmonary disease (COPD), as the pathogenesis of COPD is convoluted, and many knowledge gaps remain in the underlying cellular and molecular mechanisms. Blood eosinophil count is becoming increasingly recognized by the respiratory specialist community as a clinically relevant biomarker to help estimate effective management strategies, but its use is still widely debated.

Nathaniel Marchetti, DO, answers questions about the role of eosinophils as a biomarker to inform treatment decisions for patients with COPD. Dr Marchetti is a pulmonologist with Temple Lung Centerand a professor of clinical thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University.

Consultant360: What is the threshold for defining high and low eosinophil blood count?

Dr Nathaniel Marchetti: Most clinicians would consider a blood eosinophil count greater than 300 cells/L to be elevated.1 In in patients with COPD, there is not a low or high threshold for eosinophil counts. It can be thought of as a spectrum, with those having an eosinophil count less than 100 cells/L unlikely to respond to inhaled corticosteroids (ICS) and those with an eosinophil count greater than 300 cells/L more likely to respond.1 Most clinicians would agree that an eosinophil count greater than 300 cells/L would indicate a response to ICS. It is important to understand that this is not the only factor involved in deciding when to use ICS, and other factors, such as exacerbation frequency, need to be considered as well.

C360: Approximately what percentage of patients with COPD have evidence of eosinophilic inflammation?

NM: This question is difficult to answer.However, it appears as though individuals with COPD have more eosinophils in their blood compared with the rest of the population. Some studies estimate that 20.1% of patients with COPD will have an eosinophil count greater than 300 cell/L.2

C360: What role do eosinophils play in COPD during exacerbations and stable disease?

NM: It appears patients with higher blood eosinophil levels during stable disease have more frequent exacerbations and are likely to respond better to systemic corticosteroids.3

C360: What role might eosinophils play as a biomarker to inform treatment decisions for patients with COPD?

NM: Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines1 suggest that inhaled corticosteroids (ICS) should be used in those with an eosinophil count greater than 300 cells/L. However, this is not the only factor. If patients have more than 2 moderate exacerbations per year, they should be on an ICS regardless of eosinophil count. For those with blood eosinophils of 100 or greater, an inhaled corticosteroid can be considered.If the eosinophil count is less than 100/L, then ICS is not likely going to benefit patients.4

C360: What therapies targeting eosinophilic inflammation are available or in development?

NM: Inhaled corticosteroids are available and important in targeting eosinophilic inflammation in patients with COPD.

Biologic agents targeting eosinophilic inflammatory pathways have been studied with mixed results.These studies have targeted the ability of these medications to reduce exacerbations of COPD. Currently, it is not recommended to use these agents in COPD until better data are available. There are clinical trials ongoing with these medications to determine if they can help reduce exacerbations. Targeted pathways include IL-5, anti-TSLP, IL-33, IL-25.All of these are important in eosinophilic inflammation.4

C360: What gaps exist in the research of patients with COPD and eosinophilic inflammation? And what is next for research?

NM: Eosinophil counts vary over time.We do not entirely understand how they vary and the meaning of the variation. As mentioned, there are numerous inflammatory pathways that can be targeted to help with eosinophilic inflammation, and there are medications in development and clinical trials to find if they can help.4

References:

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The Role of Eosinophils as a Biomarker to Inform Treatment Decisions for Patients With COPD - Consultant360