Updates in Precision Oncology in Prostate and Urothelial Cancer

Abstract

Basic science, translational, and clinical genomic advances in prostate and urothelial cancer have therapeutic implications. Poly(ADP-ribose) polymerase (PARP) inhibitors target cancer cells with homologous recombination repair genomic deficiencies to induce synthetic lethality. PARP inhibitors are approved for BRCA-altered castration resistant prostate cancer treatment either as single agent or in combination with novel hormonal therapies. Another genomic target in prostate cancer is the androgen receptor, especially overcoming resistance via the AR-V7 splice variant and other mechanisms. Strategies for overcoming this resistance, including N-terminal domain inhibitors and PROTAC degraders, are under investigation. Immune checkpoint inhibition is a treatment option for metastatic castrate resistant prostate cancer for patients with mismatch repair deficiency, and neoantigen-based vaccines are under development to harness the immune system to fight prostate cancer. In urothelial cancer, FGFR3 is an important prognostic and predictive marker, often indicative of luminal tumors by gene expression profiling. Erdafitinib targets FGFR alterations and is approved for treatment of refractory metastatic urothelial cancer. Antibody-drug conjugates, including enfortumab vedotin and sacituzumab govitecan, are additional targeted approaches utilized to manage urothelial cancer.