MINNEAPOLIS/ST. PAUL (12/11/2024) — Published in Nature Communications, a new study led by the University of Minnesota Medical School and Duke University found that a DNA sequencing test for advanced prostate cancer patients can distinguish between patients with poor and favorable prognoses.
The new blood-based test — called AR-ctDETECT — is designed to detect and analyze small fragments of tumor-derived DNA in the blood of certain patients with advanced, metastatic prostate cancer.
In this new study, the AR-ctDETECT test was used to analyze DNA from more than 770 blood samples from a phase 3 clinical trial of advanced prostate cancer patients. The test identified circulating tumor DNA (ctDNA) in 59% of patients with metastatic prostate cancer. Patients with detectable circulating tumor DNA had significantly worse overall survival compared to those without. These results demonstrate the potential of the AR-ctDETECT test to provide key genetic information to tailor treatments based on similar characteristics among patients.
“Our AR-ctDETECT test, designed for prostate cancer, shows how valuable these blood tests could be in helping doctors better understand a patient's cancer and predict how the disease will progress, leading to more personalized treatment plans,” said Scott Dehm, PhD, a professor at the U of M Medical School and member of the Masonic Cancer Center.
The study concluded that detecting ctDNA using AR-ctDETECT provides critical prognostic insights for patients with metastatic prostate cancer.
“The AR-ctDETECT assay is a comprehensive panel focused on genes relevant to prostate cancer and hormone resistance, particularly the androgen receptor and critical structural alterations not currently detected by other commercial tests,” said Andrew Armstrong, MD, a professor at Duke University School of Medicine, an oncologist with Duke Cancer Institute and co-senior author on the study. “Incorporating genomic profiling into clinical decision-making may enhance personalized treatment strategies and inform the design of future clinical trials.”
“Our team demonstrated the ability of AR-ctDETECT to effectively identify distinct groups of patients based on their genomic profiles,” said Susan Halabi, PhD, a James B. Duke Distinguished Professor of Biostatistics at Duke University School of Medicine. “Notably, our study is the first to demonstrate, within a phase 3 cohort, that metastatic prostate cancer patients with positive ctDNA treated with standard therapies had worse overall survival compared to ctDNA-negative patients.”
Further research will focus on integrating genetic data from the AR-ctDETECT test with patient clinical data to improve patient prognostication. The research team also plans to evaluate whether the AR-ctDETECT test could be used to predict patient outcomes in the context of specific treatments, which could be used in the future to guide optimal therapy.
This research was funded by the National Cancer Institute, Prostate Cancer Foundation and John Black Charitable Foundation.
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About the University of Minnesota Medical School
The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu.
Journal
Nature Communications
Method of Research
Randomized controlled/clinical trial
Subject of Research
People
Article Title
AR alterations inform circulating tumor DNA detection in metastatic castration resistant prostate cancer patients
Article Publication Date
11-Dec-2024
COI Statement
MJM has served as a consultant to Lantheus, AstraZeneca, Daiichi, Convergent Therapeutics, Pfizer, ITM Isotopes, Clarity Pharmaceuticals, Blue Earth Diagnostics, POINT Biopharma, Telix, Z-Alpha, AMBRX, Flare Therapeutics, Fusion Pharmaceuticals, Curium, Transtherabio, Celgene, Arvinas, and Exelixis. His institution receives royalty payments from Telix, and research funding from Novartis, Fusion, and Astellas. HB has served as consultant/advisory board member for Janssen, Astellas, Merck, Pfizer, Foundation Medicine, Blue Earth Diagnostics, Amgen, Bayer, Oncorus, LOXO, Daicchi Sankyo, Sanofi, Curie Therapeutics, Astra Zeneca, Novartis, and has received research funding (institution) from Janssen, AbbVie/Stemcentrx, Eli Lilly, Astellas, Millennium, Bristol Myers Squibb, Circle Pharma, Daicchi Sankyo, Novartis. CJR has served as a consultant to Oric, Pfizer, Bayer, and Sanofi. ESA is a paid consultant/advisor to Janssen, Astellas, Sanofi, Dendreon, Pfizer, Amgen, Eli Lilly, Bayer, AstraZeneca, Bristol Myers Squibb, ESSA, Clovis, Merck, Curium, Blue Earth Diagnostics, Foundation Medicine, Exact Sciences and Invitae; has received research funding to his institution from Janssen, Johnson & Johnson, Sanofi, Dendreon, Genentech, Novartis, Tokai, Bristol Myers Squibb, Constellation, Bayer, AstraZeneca, Clovis and Merck; and is the coinventor of a patented AR-V7 biomarker technology that has been licensed to Qiagen. AJA reports research support (to Duke) from the NIH/NCI, PCF/Movember, DOD, Astellas, Pfizer, Bayer, Janssen, Dendreon, BMS, AstraZeneca, Merck, Forma, Celgene, Amgen, Novartis. AJA reports consulting or advising relationships with Astellas, Pfizer, Bayer, Janssen, BMS, AstraZeneca, Merck, Forma, Celgene, Myovant, Exelixis, GoodRx, Novartis, Medscape, MJH, Z Alpha, Telix. SH is a member of the Data Monitoring Committees (DMCs) for Aveo, Beigene, BMS, CG Oncology, J&J, Sanofi and was funded by grant awarded to Duke University by ASCO and Astellas. SMD has served as a paid consultant/advisor to Janssen, Bristol Myers Squibb, and Oncternal Therapeutics, and has served as principal investigator on grants awarded to the University of Minnesota by Janssen and Pfizer/Astellas. The remaining authors declare no competing interests.