Antibody-Drug Conjugates for Melanoma and Other Skin Malignancies.

While most skin malignancies are successfully treated with surgical excision, advanced and metastatic skin malignancies still often have poor long-term outcomes despite therapeutic advances. Antibody-drug conjugates (ADCs) serve as a potentially promising novel therapeutic approach to treat advanced skin cancers as they combine antibody-associated antigen specificity with cytotoxic anti-tumor effects, thereby maximizing efficacy and minimizing systemic toxicity. While no ADCs have gained regulatory approval for advanced skin cancers, several promising agents are undergoing preclinical and clinical investigation. In addition to identifying and validating skin cancer antigen targets, the key to maximizing therapeutic success is the careful development of each component of the ADC complex: antibodies, cytotoxic drugs, and linkers. It is the optimization of each of these components that will be integral in overcoming resistance, maximizing safety, and improving long-term clinical outcomes.