Cleveland Clinic researchers have discovered a novel biochemical pathway that enables prostate cancer cells to survive extensive DNA damage that normally would trigger cell death. Blocking this modulatory pathway could increase cancer cells’ vulnerability to genotoxic therapies while sparing normal cells.
Androgen deprivation therapy, which prevents androgen receptor signaling, initially is effective against advanced prostate cancer but progression eventually resumes, relying on androgen receptor’s transcriptional activity. Cleveland Clinic researchers are exploring new approaches that block this transactivation function, which may prevent or overcome resistance.
A Cleveland Clinic study shows that gene expression patterns predictive of long-term prostate cancer outcomes, such as clinical recurrence after radical prostatectomy, are observable in normal tissue adjacent to tumor and may help identify patients with aggressive disease.
Pairing abiraterone with the enzyme inhibitor dutasteride modifies abiraterone’s metabolic conversion, blocking production of a prostate tumor-promoting metabolite while aiding accumulation of another metabolite that has strong anti-tumor effects, Cleveland Clinic researchers report.
“Big data” genomic projects are helping researchers to begin isolating the androgen receptor action that drives prostate cancer to the lethal stage, providing an entirely novel target for therapy.
Incorporating the prostate cancer antigen 3 (PCA3) gene in a predictive nomogram overcomes the lack of specificity of prostate-specific antigen for prostate cancer, with the goal of reducing the number of unnecessary biopsies.
Cleveland Clinic researchers have identified a metabolite of the commonly used agent, abiraterone , that may be even better for treating advanced prostate cancer.
Molecular-based tests that predict prostate cancer’s aggressiveness have gotten a qualified endorsement from the National Comprehensive Cancer Network. The assays can be easily used to guide treatment decisions, says Cleveland Clinic’s Eric Klein, MD, boosting confidence in the choice of active surveillance for appropriate patients.
Historically, the use of upfront chemotherapy in advanced prostate cancer has faced significant challenges. But recent research results showing that systemic chemotherapy improves overall survival in patients with metastatic castration-resistant prostate cancer have changed the thinking about its use.
Stereotactic body radiation therapy and proton beam therapy have theoretical advantages over the current standard of care, intensity-modulated radiation therapy. Clinical trials will be important to determine their value.