Monthly Archives: October 2022

The discovery from UVAs Swapnil Sonkusare, PhD, and colleagues breaks new ground in our understanding of how the body regulates blood pressure.

School of Medicine researchers have identified a key contributor to high blood pressure that could lead to new treatments for a condition which affects almost half of American adults.

The discovery from UVAs Swapnil Sonkusare, PhD, and colleagues breaks new ground in our understanding of how the body regulates blood pressure. It also shows how problems with this critical biological process drive high blood pressure, also known as hypertension.

UVAs research, published in the scientific journal Circulation, identifies a new paradigm in hypertension, according to an accompanying editorial. The editorial says UVAs innovative discoveries fill major gaps in our understanding of the fundamental molecular causes of high blood pressure.

Our work identifies a new mechanism that helps maintain healthy blood pressure and shows how abnormalities in this mechanism can lead to hypertension, said Sonkusare, of UVAs Department of Molecular Physiology and Biological Physics and UVAs Robert M. Berne Cardiovascular Research Center. The discovery of a new mechanism for elevation of blood pressure could provide therapeutic targets for treating hypertension.

High blood pressure is estimated to affect more than 116 million American adults. In 2020, it contributed to or caused more than 670,000 deaths in the United States, the federal Centers for Disease Control and Prevention reports. Left unchecked, the condition can damage the heart and increase the risk for stroke and other health problems.

Our blood pressure is controlled, in part, by calcium levels in smooth muscle cells that line blood vessel walls. Smooth muscle cells transport calcium in and use it to regulate the contraction of blood vessels as needed. High blood pressure is commonly treated with calcium blockers that reduce the movement of calcium, but these medications have many side effects because they block a mechanism that is used by multiple organs in the body for carrying out normal functions. So a treatment option that targets the harmful effects of calcium but not its beneficial effects could be very helpful for patients with hypertension.

Sonkusare and his team discovered two critical and previously unknown -- signaling centers in smooth muscle cells that bring in calcium and regulate blood pressure. These nanodomains, the researchers found, act like symphony conductors for blood vessels, directing them to contract or relax as needed. These signaling centers, the researchers determined, are a key regulator of healthy blood pressure.

Further, the UVA scientists found that disruptions in this process contribute to high blood pressure. In both mouse models of the disease and hypertensive patients, the fine balance between constrictor and dilator signaling centers is lost. This caused the blood vessels to become too constricted, driving up blood pressure.

The new findings help us better understand how our bodies maintain proper blood pressure and provide enticing targets for scientists seeking to develop treatments targeting underlying causes of hypertension. Developing treatments that do not affect the beneficial effects of calcium will require additional research and a deeper understanding of the calcium-use process, but Sonkusares team is already working toward that goal.

Weve shown that smooth muscle cells use spatial separation of signaling centers to achieve constriction or dilation of arteries. We are now investigating the individual components of these signaling centers, Sonkusare said. Understanding these components will help us target them to lower or raise the blood pressure in disease conditions that show high or low blood pressure, respectively.

The researchers have published their findings in the scientific journal Circulation. The team consisted of Yen-Lin Chen, Zdravka Daneva, Maniselvan Kuppusamy, Matteo Ottolini, Thomas M. Baker, Eliska Klimentova, Soham A. Shah, Jennifer D. Sokolowski, Min S. Park and Sonkusare.

The work was supported by the American Heart Association, grant POST833691; theAmerican Physiological Society; the National Institutes of Health, grants HL146914, HL142808 and HL147555; and the Neurosurgery Research and Education Foundation.

The editorial accompanying the article was written by Rhian Touyz,MD, PhD, of the Research Institute of McGill University Health Centre at Canadas McGill University.

Sonkusare previously discovered why obesity causes high blood pressure.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog.

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UVA Discovers Key Driver of High Blood Pressure - UVA Health Newsroom

The Cancer Institute at The University of Tennessee Medical Center joins Caris' extensive network of leading cancer institutions committed to utilizing clinical data to advance patient care and outcomes

IRVING, Texas, Oct. 11, 2022 /PRNewswire/ --Caris Life Sciences(Caris), the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize health care, announced today that The University of Tennessee Medical Center's (UTMC) Cancer Institute has joined Caris' Precision Oncology Alliance (POA). The POA is a growing network of leading cancer centers across the globe that collaborate to advance precision oncology and biomarker-driven research. POA members work together to establish and optimize standards of care for molecular testing through innovative research focused on predictive and prognostic markers that improve the clinical outcomes for cancer patients.

UTMC, a Magnet recognized hospital, Level I Trauma Center and regional academic medical center, serves as a major referral center for East Tennessee, Southeast Kentucky and Western North Carolina. As the largest provider of cancer care in the region, the Cancer Institute offers the broadest spectrum of cancer specialists and services to care for the local adult population, with research as its cornerstone of knowledge.

"We are proud to join the Caris Precision Oncology Alliance," said John L. Bell, M.D., Director of the Cancer Institute at The University of Tennessee Medical Center."As cancer treatments become more sophisticated and personalized, having access to the most recent, ever-changing molecular testing helps our providers choose the best cancer treatment for each patient. It is truly an honor to join this prestigious group of institutions and make this testing available to patients in East Tennessee and beyond through cutting-edge precision oncology research."

"We're excited to welcome The University of Tennessee Medical Center's Cancer Institute into the growing Caris Precision Oncology Alliance network and look forward to collaborating with its clinicians and investigators to advance clinical and translational research," said Chadi Nabhan, M.D., MBA, FACP, Chairman of the Caris Precision Oncology Alliance. "The University of Tennessee Medical Center's addition to the POA advances our precision oncology research portfolio aiming to improve the outcomes of patients with cancer."

The Caris Precision Oncology Alliance includes 73 cancer centers and academic institutions. These institutions have early access to the extensive database and artificial intelligence platform within Caris to establish evidence-based standards for cancer profiling and advance research in cancer precision medicine. By leveraging the comprehensive genomic, transcriptomic and proteomic profiling available through Caris molecular profiling, Caris seeks to provide this network with the ability to prioritize therapeutic options and determine which clinical trial opportunities may benefit their patients. POA members are also able to integrate with a growing portfolio of biomarker directed trials sponsored by biopharma. Additionally, as a member of the POA, institutions have access to Caris CODEai, the most comprehensive data solution in the industry with cancer treatment information and clinical outcomes data for over 275,000 patients covering over 1 million data points per patient.

About Caris Life SciencesCaris Life Sciences (Caris) is the leading molecular science and technology company actively developing and delivering innovative solutions to revolutionize healthcare and improve patient outcomes. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced artificial intelligence (AI) and machine learning algorithms, Caris has created the large-scale clinico-genomic database and cognitive computing needed to analyze and unravel the molecular complexity of disease. This information provides an unmatched resource and the ideal path forward to conduct the basic, fundamental research to accelerate discovery for detection, diagnosis, monitoring, therapy selection and drug development to improve the human condition.

With a primary focus on cancer, Caris' suite of market-leading molecular profiling offerings assesses DNA, RNA and proteins to reveal a molecular blueprint that helps patients, physicians and researchers better detect, diagnose and treat patients. Caris' latest advancement is a blood-based, circulating nucleic acids sequencing (cNAS) assay that combines comprehensive molecular analysis (Whole Exome and Whole Transcriptome Sequencing from blood) and serial monitoring making it the most powerful liquid biopsy assay ever developed.

Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Denver, Tokyo, Japan and Basel, Switzerland. Caris provides services throughout the U.S., Europe, Asia and other international markets. To learn more, please visitCarisLifeSciences.comor follow us on Twitter (@CarisLS).

About The University of Tennessee Medical Center:The mission of The University of Tennessee Medical Center (UTMC), a Magnet recognized hospital also certified by The Joint Commission as a Comprehensive Stroke Center, is to serve through healing, education and discovery. UTMC is a 710-bed, not-for-profit academic medical center, with a regional network of primary care and specialty care physicians and practices as well as outpatient regional health centers and urgent care locations throughout its 21-county primary service area. The medical center, the region's ACS-verified Level I Trauma Center and state designated regional perinatal referral center with a Level III private room NICU, is one of the largest employers in Knoxville. UTMC features nine Centers of Excellence, including the Brain & Spine Institute, Cancer Institute, Emergency & Trauma Center, Heart Lung Vascular Institute, Orthopaedic Institute, Center for Complex Medicine, Center for Perioperative Medicine, Primary Care Collaborative and Center for Women & Infants. VisitUTMedicalCenter.orgfor more information.

Caris Life Sciences Media Contact: Lisa Burgner[emailprotected]214.294.5606

The University of Tennessee Medical CenterMedia Contact:Laura Dean[emailprotected]865.305.6082

SOURCE Caris Life Sciences

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Caris' Precision Oncology Alliance Welcomes The Cancer Institute at The University of Tennessee Medical Center - PR Newswire

Aside from catching Covid itself, many other factors could increase the risk of someone developing long Covid a chronic condition that develops after acute Covid infections and is characterized by a variety of symptoms, such as fatigue, breathing problems, or brain fog. Some of these risk factors include having asthma, type 2 diabetes, autoimmune conditions, or being female.

Now, a team of scientists led by Harvard University has found that patients with arthritis who developed long Covid showed evidence of an underwhelming antibody response to SARS-CoV-2, but a massive antibody response to OC43 one of the several endemic coronaviruses that cause common colds.

The researchers tested the blood of 43 patients who had arthritis or a similar condition before the pandemic, and discovered that, when their immune systems were exposed to SARS-CoV-2, they responded with OC43 antibodies which, although similar, were less than ideal in fighting the novel coronavirus, leading to chronic inflammation and other long Covid symptoms.

According to Eric Topol, a professor of Molecular Medicine at Scripps Research, these new findings come in a very interesting report that adds to the possible underpinnings of long Covid. While previous research investigated the relationship between prior infections with the Epstein-Barr virus and other pathogens and long Covid risk factors, this is the first study to assess the role common cold may play in the development of this debilitating conditions.

However, the researchers warned that that are multiple categories of long Covid with, perhaps, different triggers for each type (aside from Covid itself). Thus, although prior infection with this common cold may play a role in arthritis patients with long Covid, it may or may not play a similar role in other categories of patients. Nonetheless, this discovery could serve as a way of identifying long Covid risk levels in arthritis patients and possibly find new ways of treating it.

A pre-print version of the study is published in medRxiv.

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

By Andrei Ionescu, Earth.com Staff Writer

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Common cold may increase the risk of long Covid - Earth.com

About the position

We have a vacancy for a postdoctoral researcher at the Department of Clinical and Molecular Medicine.

The position is within the project Liquid biopsies for identifying relapsing lung cancer, which is using profiles of circulating tumour DNA (ctDNA) and microRNAs (miRNAs) to develop a classification system for identifying lung cancer patients with risk of relapse after curative therapy. The project is a collaboration between NTNU, St. Olavs hospital, and University of Troms, and the multidisciplinary project group include physicians and researchers of oncology, pathology, bioinformatics, and molecular biology.

The postdoc position will focus on bioinformatics analyses of ctDNA and miRNA data generated from repeated blood samples taken from lung cancer patients before, during, and after treatment. The data analyses will include processing of raw sequencing data, testing for associations between miRNA or ctDNA profiles and clinically relevant parameters, and developing models that integrate ctDNA and miRNA profiles for predicting relapse. The position is available at the bioinformatics and gene regulation research group and will report to professor Pl Strom.

Duties of the position

The postdocs main responsibility will be bioinformatics analyses of high throughput genomics data from lung cancer patients, but the position will also involve the following tasks:

Requiredselectioncriteria

The appointment is to be made in accordance withRegulations on terms of employment for positions such as postdoctoral fellow, Ph.D Candidate, research assistant and specialist candidate.

Preferred selection criteria

Personal characteristics

Weoffer

Salary and conditions

As a Postdoctoral Fellow (code 1352) you are normally paid from gross NOK 563 500 per annum before tax, depending on qualifications and seniority. From the salary, 2% is deducted as a contribution to the Norwegian Public Service Pension Fund

The period of employment is 2years.

The engagement is to be made in accordance with the regulations in force concerningState Employees and Civil Servants, and the acts relating to Control of the Export of Strategic Goods, Services and Technology. Candidates who by assessment of the application and attachment are seen to conflict with the criteria in the latter law will be prohibited from recruitment to NTNU.

It is a prerequisite you can be present at and accessible to the institution on a daily basis.

About the application

The application and supporting documentation to be used as the basis for the assessment must be in English.

Publications and other scientific work must follow the application. Please note that applications are only evaluated based on the information available on the application deadline. You should ensure that your application shows clearly how your skills and experience meet the criteria which are set out above.

If, for any reason, you have taken a career break or have had an atypical career and wish to disclose this in your application, the selection committee will take this into account, recognizing that the quantity of your research may be reduced as a result.

The application must include:

If all, or parts, of your education has been taken abroad, we also ask you to attach documentation of the scope and quality of your entire education. Description of the documentation required can be found here. If you already have a statement from NOKUT, please attach this as well.

Joint works will be considered. If it is difficult to identify your contribution to joint works, you must attach a brief description of your participation.

In the evaluation of which candidate is best qualified, emphasis will be placed on education, experience and personal and interpersonal qualities. Motivation, ambitions, and potential will also count in the assessment of the candidates.

NTNU is committed to following evaluation criteria for research quality according toThe San Francisco Declaration on Research Assessment - DORA.

General information

Working at NTNU

NTNU believes that inclusion and diversity is a strength. We want our faculty and staff to reflect Norways culturally diverse population and we continuously seek to hire the best minds. This enables NTNU to increase productivity and innovation, improve decision making processes, raise employee satisfaction, compete academically with global top-ranking institutions and carry out our social responsibilities within education and research. NTNU emphasizes accessibility and encourages qualified candidates to apply regardless of gender identity, ability status, periods of unemployment or ethnic and cultural background.

NTNU is working actively to increase the number of women employed in scientific positions and has a number ofresources to promote equality.

The city of Trondheimis a modern European city with a rich cultural scene. Trondheim is the innovation capital of Norway with a population of 200,000.The Norwegian welfare state, including healthcare, schools, kindergartens and overall equality, is probably the best of its kind in the world. Professional subsidized day-care for children is easily available. Furthermore, Trondheim offers great opportunities for education (including international schools) and possibilities to enjoy nature, culture and family life and has low crime rates and clean air quality.

As an employeeatNTNU, you mustat all timesadhere to the changes that the development in the subject entails and the organizational changes that are adopted.

A public list of applicants with name, age, job title and municipality of residence is prepared after the application deadline. If you want to reserve yourself from entry on the public applicant list, this must be justified. Assessment will be made in accordance withcurrent legislation. You will be notified if the reservation is not accepted.

If you have any questions about the position, please contact Professor Pl Strom, telephone +47 98203874, emailpal.satrom@ntnu.no. If you have any questions about the recruitment process, please contact HR Advisor Vebjrn F. Andreassen, e-mail:vebjorn.andreassen@ntnu.no

If you think this looks interesting and in line with your qualifications, please submit your application electronically via jobbnorge.no with your CV, diplomas and certificates attached. Applications submitted elsewhere will not be considered.Upon request, you must be able to obtain certified copies of your documentation.

Application deadline:19.10.22

NTNU

NTNU - knowledge for a better world

The Norwegian University of Science and Technology (NTNU) creates knowledge for a better world and solutions that can change everyday life.

The Department of Clinical and Molecular Medicine (IKOM):

The Department of Clinical and Molecular Medicine (IKOM) is NTNUs largest department, with 450 employees. Our research and teaching help to improve treatment and health.

IKOM has expertise in basic, clinical and translational research within broad disciplinary areas. We study childrens and womens health, cancers, blood disorders and infectious diseases, gastroenterology, inflammation, metabolic disorders, laboratory sciences and medical ethics. The Department offers teaching in medicine at masters and PhD level. We also offer continuing education for employees in the health services.

Deadline19th October 2022EmployerNTNU - Norwegian University of Science and TechnologyMunicipalityTrondheimScopeFulltimeDuration ProjectPlace of service

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Postdoctoral Fellow in Lung Cancer Genomics job with NORWEGIAN UNIVERSITY OF SCIENCE & TECHNOLOGY - NTNU | 311727 - Times Higher Education

Merus N.V.

MCLA-129 observed to be well tolerated with preliminary evidence of anti-tumor activity during dose escalation phase

Initial recommended phase two dose set at 1500 mg with dose expansion ongoing

Poster presentation with additional data at ENA available on October 26 at 9am CET/3am ET, and presented on October 28, 2022, 10:00-15:00 CET

Investor call to discuss a MCLA-129 program update on October 26 at 13:30 CET/7:30am ET

UTRECHT, The Netherlands and CAMBRIDGE, Mass., Oct. 12, 2022 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), today announced the publication of the abstract highlighting interim data from the ongoing phase 1/2 trial of the bispecific antibody MCLA-129 on the 34th EORTC/NCI/AACR Symposium on Molecular Targets and Cancer Therapeutics (ENA Symposium) website. MCLA-129 is a fully human IgG1 Biclonics bispecific antibody that binds to EGFR and c-MET and is being investigated in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors. This phase 1/2 study has completed the dose escalation phase and is on-going in the dose expansion phase.

The poster will be presented at the 34th ENA Symposium in Barcelona, Spain on Friday, October 28, 2022, 10:00-15:00 CET, and will be available online Wednesday, October 26, 2022. The poster presentation will include additional interim clinical data from this dose escalation cohort.

We are encouraged by the promising initial clinical data for MCLA-129 presented in the abstract and are looking forward to providing additional clinical data from the dose escalation cohort in the poster presentation at the ENA Symposium, said Dr. Andrew Joe, Chief Medical Officer at Merus. We also intend to share a MCLA-129 program update on our upcoming conference call.

The reported interim data in the abstract are from the phase 1/2 trial of MCLA-129 in patients with advanced NSCLC and other solid tumors.

Story continues

Information and observations in the abstract include:

As of the May 8, 2022 cutoff date, 20 patients were treated with MCLA-129 across doses of 100, 300, 600, 1000, and 1500 mg every two weeks

Median age of patients was 65 years (range 43-79)

Tumor types enrolled included:

14 patients with EGFR mutant (mt) NSCLC (4 L858R, 8 Del19, 1 exon 20 insertion, 1 other)

2 patients with c-MET exon 14 mt NSCLC

1 patient with c-MET amplified gastric adenocarcinoma

1 patient with squamous cell esophageal cancer

2 patients with head and neck squamous cell carcinoma

13 patients were evaluable for response with preliminary signs of anti-tumor activity observed:

Median duration of treatment was 8 weeks (range 3.4- 29.3) with 11 patients still on treatment at the cutoff date

Safety:

No dose limiting toxicity was observed and maximum tolerated dose was not reached

The most frequently reported adverse event (AE) was infusion related reaction (IRR)

18 of 20 pts (90%) reported IRR after first dose, all but one were mild or moderate (grade 1-2)

All but one infusion were completed on the same day

No treatment discontinuations due to AE

No interstitial lung disease was observed

Recommended initial phase 2 dose for expansion is 1500 mg every two weeks. The expansion cohorts are enrolling.

Dose-dependent depletion of soluble EGFR and c-MET was observed

In doses ranging from 600-1500 mg every two weeks, MCLA-129 demonstrated linear pharmacokinetics

Mean serum concentrations at 1500 mg every two weeks dose are modeled to be above that required for >95% target engagement of cell-bound EGFR and c-MET throughout the dosing period

Presentation Details:

Title: MCLA-129, a human anti-EGFR and anti-c-MET bispecific antibody, in patients with advanced NSCLC and other solid tumors: an ongoing phase 1/2 studyFirst author: Prof. Sai-Hong Ignatius Ou, Department of Medicine, Division of Hematology Oncology, University of California Irvine School of Medicine, USSession: New Therapies in Immuno OncologyDate: Friday, October 28, 2022 Time: 10:00-15:00 CETAbstract #: 341Poster #: PB121

The poster will be available at the start of the conference on October 26, 2022and on-demand throughout the conference on the conferencewebsite. The poster will also be available on the Merus website contemporaneously.

Company Conference Call and Webcast Information

Merus will hold a conference call and webcast for investors on Wednesday, October 26, 2022 at 13:30 CET/7:30am ET to discuss the MCLA-129 initial clinical data and provide a program update. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time.

Date: October 26, 2022Webcast link: available on our websiteDial-in: Toll-free: 1 (800) 715-9871 / International: 1 (646) 307-1963Conference ID: 1694377

About MCLA-129MCLA-129 is an antibody-dependent cellular cytotoxicity-enhanced Biclonics that is designed to inhibit the EGFR and c-MET signaling pathways in solid tumors. Preclinical data have shown that MCLA-129 can effectively treat TKI-resistant non-small cell lung cancer (NSCLC) in xenograft models of cancer. MCLA-129 is designed to have two complementary mechanisms of action: blocking growth and survival pathways to stop tumor expansion and recruitment and enhancement of immune effector cells to eliminate the tumor.

About Merus N.V.Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics. Multiclonics are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus website, http://www.merus.nland https://twitter.com/MerusNV.

Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding MCLA-129s mechanisms of action; the impact of observations concerning any interim clinical data, including on future results or development plans; any planned clinical or program updates; and potential of the MCLA-129 Biclonics in preclinical or clinical development to treat cancer.

These forward-looking statements are based on managements current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or Biclonics, Triclonics and multispecific antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the COVID-19 pandemic; we may not identify suitable Biclonics or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks.

These and other important factors discussed under the caption Risk Factors in our Quarterly Report on Form 10-Q for the period ended June 30, 2022 filed with the Securities and Exchange Commission, or SEC, on August 8, 2022, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.

Multiclonics, Biclonics and Triclonics are a registered trademarks of Merus N.V.

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Merus Announces Publication of Abstract on MCLA-129 at the 34th EORTC/NCI/AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics - Yahoo...

A molecular test called PancreaSeq accurately classifies pancreatic cysts as potentially cancerous or benign, according to a large, multi-center study led by University of Pittsburgh School of Medicine and UPMC researchers.

Published in Gastroenterology, the prospective study of more than 1,800 patients found that incorporating molecular markers improved the accuracy of diagnoses compared with current guidelines based on imaging of cysts.

Based on the results of this study, molecular testing of pancreatic cysts is poised to enter international consensus guidelines for the diagnosis of pancreatic cysts and early detection of pancreatic cancer, said co-senior author Aatur Singhi, M.D., Ph.D., associate professor of pathology at Pitt and UPMC Hillman Cancer Center investigator. Our hope is that PancreaSeq will not only improve early detection of pancreatic cancer but also avoid overtreatment and unnecessary surgery of non-cancerous cysts.

Up to 15% of the U.S. population will develop a pancreatic cyst at some point in their lives. Most of these cysts are benign, but a small fraction will transform into cancer.

Although rare, pancreatic cancer is a deadly disease: Most patients will die within a few years of diagnosis, said Singhi. The only way we can improve outcomes for pancreatic cancer is to find better treatments or detect it earlier. Here at UPMC, our focus has been addressing both of these issues, and especially improving early-stage detection efforts.

Pitt developed PancreaSeq, which accurately distinguishes benign cysts from those that could become cancerous by sequencing 22 pancreatic cyst-associated genes.

To capture the true population of pancreatic cyst patients and confirm that PancreaSeq can be applied in a clinical setting, the new multi-center study included 1,832 patients from 31 institutions. Using a prospective study design, the researchers analyzed molecular markers in pancreatic cyst fluid collected from patients and followed their outcomes for two years.

Pancreatic cysts can be broadly categorized as non-mucinous, which are benign, and mucinous, which have the potential to give rise to pancreatic cancer.

Based on mutations in genes called KRAS and GNAS, PancreaSeq diagnosed mucinous cysts accurately in 90% of cases, making it a highly sensitive test. It did not identify any false positives, meaning that it had a specificity of 100%.

There is a very low likelihood of mucinous cysts giving rise to cancer, but accurately identifying this type of cyst is important because it gives us a window of opportunity to monitor patients and prevent pancreatic cancer from developing, said Singhi.

Among mucinous cysts, the test accurately identified those that had advanced to cancer in 88% of cases and with a specificity of 98%. When the researchers included another type of analysis evaluation of cells under the microscope for cancer-associated changes the test sensitivity improved to 93% and specificity remained high at 95%.

The test also performed well in detecting non-mucinous cysts and another type of lesion called pancreatic neuroendocrine tumors. Also known as PanNETs, these tumors are usually benign, but can be lethal if they metastasize to other parts of the body.

This study lays the foundation for developing prognostic biosignatures for PanNETs so that we can identify which tumors will metastasize and which wont, said Singhi.

Current guidelines for assessing whether a pancreatic cyst is cancerous mostly rely on imaging of features such as size and growth rate. The researchers found that PancreaSeq distinguished different types of cysts with higher accuracy than traditional forms of surveillance and current pancreatic cyst guidelines.

According to Singhi, the findings from this study will inform international consensus guidelines for treatment of pancreatic cysts, adding molecular testing to forthcoming updated recommendations.

This test developed at UPMC is going to make a big difference in how we classify and manage patients moving forward, said Singhi. Our hope is that PancreaSeq prevents overtreatment but at the same time doesnt miss pancreatic cancer.

An expanded version of PancreaSeq that includes a broader array of biomarkers is now available to patients both within the U.S. and internationally. Samples are collected at local centers and are sent to UPMC for testing and analysis. The researchers are now applying for broad insurance coverage, which they hope to have approved by the end of the year.

Reference: Singhi A, et al. Prospective, multi-institutional, real-time next-generation sequencing of pancreatic cyst fluid reveals diverse genomic alterations that improve the clinical management of pancreatic cysts. Gastroenterology. 2022.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Molecular Test Could Improve Early Detection of Pancreatic Cancer - Technology Networks