Antibody-drug conjugates in prostate cancer: Emerging strategies to enhance therapeutic index and current clinical landscape (Review)

The global incidence of prostate cancer (PCa) is rising. Localized PCa can be managed through surgical intervention or radiotherapy, but certain patients may experience recurrence or develop metastatic disease following localized treatment. Despite aggressive therapeutic approaches, the majority of metastatic patients with PCa will eventually progress to metastatic castration-resistant PCa, with limited treatment alternatives and a dismal prognosis. The treatment options for advanced PCa are continuously evolving, yet there remains a demand for further innovative therapeutic approaches. Antibody-drug conjugates (ADCs) represent a novel class of targeted medications comprising a humanized monoclonal antibody, a linker and a cytotoxic payload. ADCs primarily bind to antigens that are upregulated on the surface of PCa cells but are minimally expressed on normal cells. At present, a variety of targets for ADCs have been identified in the treatment of PCa, encompassing prostate-specific membrane antigen, STEAP family member 1, trophoblast cell-surface antigen 2, CD46, B7-H3, tissue factor and delta-like protein 3, each with one or more specific ADC that has shown encouraging results in the PCa field. In the present review, the developmental course, composition and mechanism of action of ADCs are explored, with a specific focus on recently published studies and ongoing trials aimed at investigating the efficacy and safety of ADCs in treating PCa. Lastly, ongoing challenges in ADC development and corresponding strategies to combat them are discussed.