Introductory Chapter: An Overview of Urologic Cancers – Molecular Mechanisms and Emerging Therapies

Epidemiology, pathology, and molecular basis of urologic cancersUrologic cancers represent a diverse spectrum of malignancies within the genitourinary tract, posing a significant global health burden.The most prevalent include prostate, kidney, and bladder cancers, whereas penile, testicular, and urethral cancers are rarer but clinically significant.According to GLOBOCAN 2022, prostate cancer ranks as the second most diagnosed malignancy in men and the fifth leading cause of male cancer-related deaths, with approximately 1,467,854 new cases and 397,430 deaths, while bladder cancer ranks ninth globally with 614,298 cases and 220,596 deaths [1].Histopathologically, each cancer type displays distinct features: Prostate cancer typically originates in the acinar epithelium of the peripheral zone, with high-grade prostatic intraepithelial neoplasia (HGPIN) acting as a precursor lesion characterized by epithelial proliferation with nuclear atypia and intact basal cells [2, 3].Renal cell carcinoma (RCC), arising from renal tubular epithelium, can spread via the lymphatics or renal vein and is subtyped into clear-cell (von Hippel-Lindau, VHL alterations), papillary (MET or fumarate hydratase, FH alterations), and chromophobe variants (chromosomal and mitochondrial abnormalities) [2,4].Urothelial carcinoma (UC) originates in the bladder and ureter's epithelial lining, presenting as non-muscleinvasive (Ta, T1, carcinoma in situ) or muscle-invasive forms (≥T2) with metastasis potential [2].Penile squamous cell carcinoma, though rare, is aggressive and linked to HPV infection, phimosis, and chronic inflammation, with predictable lymphatic spread to the inguinal-femoral regions [5].Testicular germ-cell tumors such as seminomas and non-seminomas primarily affect young men and respond well to cisplatinbased combination therapy, achieving high cure rates [6].Urethral carcinoma varies histologically according to site and sex, encompassing urothelial, squamous, or adenocarcinomatous elements (Figure 1 and Table 1) [2].Molecularly, these malignancies exhibit shared hallmarks of genomic instability and pathway dysregulation.In RCC, VHL loss causes hypoxia-inducible factor (HIF) stabilization, promoting angiogenesis via vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) activation.Papillary RCC features MET activation or FH deficiency, while chromophobe RCC shows chromosomal deletions and mitochondrial