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Researchers Identify Genetic Factors Associated With Drug Resistance in Prostate Cancer




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Researchers identify genetic factors linked to drug resistance in prostate cancer.

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In a new study published in Molecular Cancer Researchh, Mayo Clinic researchers have identified critical genomic changes in response to abiraterone acetate/prednisone, a standard treatment option for men with progressive, incurable, castration-resistant prostate cancer.

“We have identified a potential strategy for both responders and non-responders to the drug that may help men overcome resistance and prolong survival,” says Liu Wang, MD, director of Bernard and Edith Waterman, Pharmaceutical Genomics Program, Mayo Clinic Center for Individualized Medicine. . Dr. Wang is the study’s corresponding author.

Dr. Wang explains that while many drug options are available to control disease progression, many questions remain about which drugs to use in individual cases. Also, predictive biomarkers of drug resistance and sensitivity remain primarily unknown.

Abiraterone acetate is a standard treatment option for men with castration-resistant prostate cancer. However, the response rate is limited, there are no known biomarkers that predict the prognosis, and alternative treatments for those who have failed treatment are not available.


In the Clinically Enhanced Genome Therapy for Prostate Cancer Study, also known as PROMOTE, Mayo researchers uncovered the DNA sequence associated with the response to abiraterone acetate to identify additional treatment options for men with advanced prostate cancer resistant to all standard treatments. They identified an 11-gene drug panel that provided a new tool for individualizing therapy for abiraterone acetate. A genetic test panel is a lab test that looks at a selection of genes. The 11-gene panel predicted a worse prognosis for the subgroup 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 sequencing data from 83 patients who had diffuse biopsies before and after 12 weeks of abiraterone acetate/prednisone treatment. They identified genomic changes 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 determine the mechanisms of acquired resistance,” says Hugh Secot, PhD, a bioinformatics scientist at Mayo Clinic and lead author of the study. “These findings may aid the selection of alternative therapies in the subgroup of ibraterone acetate-resistant patients with the highest risk of having the worst outcomes.”

Dr. Sekot says biomarkers based on the stage-specific landscape of genetic changes in prostate cancer are under investigation.

“Further studies will be needed to test these drug treatments to overcome abiraterone acetate/prednisone resistance and to identify subgroups of non-responders,” says Dr. “Our goal is to incorporate these into clinical practice for clinicians and patients with castration-resistant prostate cancer.”

Prostate cancer is the most common type of malignancy diagnosed in the United States, with more than 268,490 new diagnoses annually and an estimated 34,500 deaths. It’s the second leading cause of cancer death in men, according to the National Cancer Institute’s Epidemiology and End Results Program.

The PROMOTE study is a collaboration between the Mayo Clinic Individualized Medicine Center and the Mayo Clinic Comprehensive Cancer Center.

Reference: Sicotte H, Kalari KR, Qin S, et al. Molecular appearance changes in castration-resistant prostate cancer patients before and after treatment with abiraterone/prednisone. precision mall cancer. 2022: MCR-22-0099. doi: 10.1158/1541-7786.MCR-22-0099

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