Current Oncology

Antibody–drug conjugates (ADCs) have reshaped the treatment landscape of urothelial carcinoma (UC) by enabling selective delivery of highly potent cytotoxic agents to tumor cells. Enfortumab vedotin, sacituzumab govitecan, and HER2-directed ADCs have demonstrated meaningful clinical activity across metastatic and earlier disease settings, with enfortumab vedotin plus pembrolizumab now established as a first-line standard of care. Despite these advances, therapeutic responses remain heterogeneous, and resistance frequently limits durability. This review summarizes current knowledge on predictors of response and mechanisms of resistance to ADCs in UC, highlighting the roles of target antigen expression and heterogeneity, genomic alterations, payload sensitivity, drug efflux transporters, and tumor microenvironmental factors. We discuss emerging biomarkers beyond antigen abundance, patterns of cross-resistance and treatment sequencing, and evolving strategies to overcome resistance, including next-generation ADC design and rational combination therapies. Advancing biomarker-driven patient selection and addressing mechanisms of resistance will be critical to maximizing the durability and clinical impact of ADCs in urothelial carcinoma.

Background: People living with HIV (PLWH) have historically been excluded from cancer clinical trials, prompting the 2017 ASCO–Friends of Cancer Research recommendations to limit unjustified exclusions and promote equitable access. This study evaluated how Canadian Cancer Trials Group (CCTG) protocols align with these recommendations. Methods: We conducted a cross-sectional review of CCTG active trial protocols, abstracting HIV eligibility language and trial characteristics, and assessing associations using Chi-square tests. Results: Of 136 trials activated between 1999 and 2025, 81.6% involved solid tumors, 63.2% systemic therapy interventions, and 61.5% phase III designs. PLWH were included, not mentioned or excluded in 49/136 (36%), 55/136 (40.4%) and 32/136 (23.5%) respectively, with justification in 7/32 (21.9%). In multivariable analyses, exclusion was more likely in trials of immune checkpoint blockade therapy (p = 0.039) and those with industry support (p = 0.014). Adjusted models showed that both industry sponsorship and immune checkpoint blockade independently reduced HIV trial inclusion. Conclusions: Most CCTG-associated trials were inclusive or neutral toward PLWH; however, a proportion still excluded them, often without justification. This first national assessment evaluating adoption of ASCO Friends of Cancer Research–HIV guidance establishes a Canadian benchmark for equitable trial design and future research as both cancer and HIV therapies continue to evolve.

According to the WHO classification of tumors, neuroendocrine neoplasms (NENs) of the esophagus are esophageal “epithelial neoplasms with neuroendocrine differentiation, including well-differentiated neuroendocrine tumours (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs)—an umbrella category including mixed adenoneuroendocrine carcinoma (MANEC)” [...]