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“Researchers identify genetic factors associated with drug resistance in prostate cancer”
In a new study published in Molecular cancer researchh, Mayo Clinic researchers identified critical genomic changes in response to abiraterone/prednisone acetate, a standard treatment option for men with progressive, incurable, castration-resistant prostate cancer .
“We have identified a potential strategy for drug responders and non-responders that could help men overcome resistance and prolong survival,” says Liewei Wang, MD, Ph.D., Bernard and Edith Waterman, director from the Pharmacogenomics Program at the Mayo Clinic Research Center. Individualized medicine. Dr. Wang is the corresponding author of the study.
Dr. Wang explains that although several drug choices are available to control the progression of the disease, many questions remain about which drugs to use in individual cases. Moreover, predictive biomarkers of drug resistance and susceptibility remain essentially unknown.
Abiraterone acetate is a standard treatment option for men with castration-resistant prostate cancer. However, the response rate is limited, no known biomarker predicts prognosis, and alternative therapies for those who have failed treatment are not available.
In the Prostate Cancer Medically Optimized Genome Enhanced Therapy study, also known as PROMOTE, Mayo researchers revealed DNA sequences associated with the response to abiraterone acetate to identify treatment options supplements for men with advanced prostate cancer resistant to all standard therapies. They identified an 11-gene drug panel that provided a new tool to individualize abiraterone acetate treatment. A genetic testing panel is a laboratory test that examines a selected group of genes. The 11-gene panel predicted a worse prognosis for a subset of primary or metastatic patients enrolled in the study.
In the next step of their analysis in this prospective study, the researchers analyzed whole exome sequencing and RNA sequence data from 83 patients with metastatic biopsies before and after 12 weeks of d-acetate treatment. abiraterone/prednisone. They identified genomic alterations associated with acquired resistance after 12 weeks of this treatment.
“We analyzed the post-treatment genomic landscape of metastatic biopsies in these patients with metastatic castration-resistant prostate cancer to identify mechanisms of acquired resistance,” explains Hugues Sicotte, Ph.D., bioinformatician at the Mayo Clinic and lead author of the study. “These results may help select alternative therapies in a subset of abiraterone acetate-resistant patients with the highest risk of having the poorest outcomes.”
Dr. Sicotte says biomarkers based on the stage-specific landscape of genomic changes in prostate cancer are being investigated.
“Further studies will be needed to test these drug treatments to overcome abiraterone/prednisone acetate resistance and define subgroups of non-responders,” says Dr. Sicotte. “Our goal is to integrate them into the clinical practice of physicians and patients with castration-resistant prostate cancer.”
Prostate cancer is the most commonly diagnosed solid organ malignancy in the United States, with more than 268,490 new diagnoses annually and approximately 34,500 deaths. It is the second leading cause of cancer death in men, according to the National Cancer Institute’s Epidemiology and Endpoints Surveillance Program.
The PROMOTE study is a collaboration between the Mayo Clinic Center for Individualized Medicine and the Mayo Clinic Comprehensive Cancer Center.
Reference: Sicotte H, Kalari KR, Qin S, et al. Molecular profile changes in patients with castration-resistant prostate cancer before and after treatment with abiraterone/prednisone. Mol Cancer Res. 2022: MCR-22-0099. doi: 10.1158/1541-7786.MCR-22-0099
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