| Abstract: |
Except for skin cancer, prostate cancer (PC) is the most common cancer in man. Localized PCs are usually managed with radical prostatectomy or radiation therapy +/- androgen deprivation therapy (ADT) and have an excellent prognosis. For metastatic castration-resistant PC (mCRPC), the median survival remains dismal despite the advances in chemotherapy, novel androgen receptor signaling inhibitors (ARSIs), and radiopharmaceuticals. Fortunately, genomic sequencing has expanded the genetic landscape of PC with various genetic alterations which lead to activation of several signal transduction pathways. The clinically actionable pathways include androgen receptor (AR)-signaling, DNA repair, prostate-specific membrane antigen, cell cycle, PTEN/PI3K/AKT/mTOR, and RAS/RAF/MEK/ERK (MAPK) pathways. FDA-approved targeting agents are being tested in clinical trials to evaluate their efficacies and have yielded some preliminary results. Cancers in the bladder and kidney are two other important cancers in the genitourinary system. Based on the molecular signatures of bladder cancers, urothelial cancers are targeted with the agents inhibiting the FGFR2 and HER2 signaling pathways and immunocheck points. Renal cell carcinoma (RCC) constitutes the main cancer type of the kidney. Compared to other cancer types with oncogenes driving tumorigenesis, most of the somatic mutations identified in RCC involve tumor suppressor genes, posing a critical challenge for therapeutic targeting. Molecular studies in penile carcinoma and testicular tumors also show promises in future targeted therapies. © 2025 selection and editorial matter, Xianfeng F. Zhao and Shiyong Li. |
