Antibody drug conjugate development in gastrointestinal cancers: hopes and hurdles from clinical trials

Abstract

Gastrointestinal (GI) cancers represent the leading cause of cancer-related mortality worldwide. Antibody drug conjugates (ADCs) are a rapidly growing new class of anti-cancer agents which may improve GI cancer patient survival. ADCs combine tumour-antigen specific antibodies with cytotoxic drugs to deliver tumour cell specific chemotherapy. Currently, only two ADCs [brentuximab vedotin and trastuzumab emtansine (T-DM1)] have been Food and Drug Administration approved for the treatment of lymphoma and metastatic breast cancer, respectively. Clinical research evaluating ADCs in GI cancers has shown limited success. In this review, we will retrace the relevant clinical trials investigating ADCs in GI cancers, especially ADCs targeting human epidermal growth receptor 2, mesothelin, guanylyl cyclase C, carcinogenic antigen-related cell adhesion molecule 5 (also known as CEACAM5) and other GI malignancy specific targets. We will review potential hurdles for their success and provide new perspective for future treatment.

Keywords

Antibody drug conjugates / human epidermal growth receptor 2 / mesothelin / guanylyl cyclase C / carcinogenic antigen-related cell adhesion molecule 5 gastric cancer / colorectal cancer / pancreatic cancer / T-DM1 / DS-8201a

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