Antibody-drug conjugates for hepato-pancreato-biliary malignancies: “Magic bullets” to the rescue?

Highlights•Current schemes of systemic treatment for HPB malignancies offer a mediocre, at best, survival benefit.•ADCs merge the intricate selectivity and specificity of monoclonal antibodies with the cytotoxicity of attached payloads.•Several intricate characteristics of their design make them a highly promising class of drugs for HPB cancers.•Recent preclinical studies have demonstrated notable antineoplastic effects in vitro and in vivo.•Several agents have been propelled into clinical trial evaluation with promising early results.AbstractHepato-Pancreato-Biliary (HPB) malignancies constitute a highly aggressive group of cancers that have a dismal prognosis. Patients not amenable to curative intent surgical resection are managed with systemic chemotherapy which, however, confers little survival benefit. Antibody-Drug Conjugates (ADCs) are tripartite compounds that merge the intricate selectivity and specificity of monoclonal antibodies with the cytodestructive potency of attached supertoxic payloads. In view of the unmet need for drugs that will enhance the survival rates of HPB cancer patients, the assessment of ADCs for treating HPB malignancies has become the focus of extensive clinical and preclinical investigation, showing encouraging preliminary results. In the current review, we offer a comprehensive overview of the growing body of evidence on ADC approaches tested for HPB malignancies. Starting from a concise discussion of the functional principles of ADCs, we summarize here all available data from preclinical and clinical studies evaluating ADCs in HPB cancers.