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Wu et al. Cancer Drug Resist 2018;1:204-18 Cancer
DOI: 10.20517/cdr.2018.16 Drug Resistance

Review Open Access

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

Xiaorong Wu, Thomas Kilpatrick, Ian Chau

Department of Medical oncology, Royal Marsden Hospital NHS foundation trust, Sutton SM2 5PT, UK.
Correspondence to: Dr. Ian Chau, Department of Medical Oncology, Royal Marsden Hospital NHS foundation trust, Downs
Road, Sutton SM2 5PT, UK. E-mail: ian.chau@rmh.nhs.uk

How to cite this article: Wu X, Kilpatrick T, Chau I. Antibody drug conjugate development in gastrointestinal cancers: hopes
and hurdles from clinical trials. Cancer Drug Resist 2018;1:204-18. http://dx.doi.org/10.20517/cdr.2018.16

Received: 31 Aug 2018 First Decision: 8 Oct 2018 Revised: 13 Nov 2018 Accepted: 16 Nov 2018 Published: 19 Dec 2018

Science Editors: Elisa Giovannetti, Jose A. Rodriguez Copy Editor: Cui Yu Production Editor: Huan-Liang Wu

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

INTRODUCTION
Gastrointestinal (GI) cancers comprise a heterogeneous group of cancers that include gastric, oesophageal,
pancreatic, hepatobiliary, colorectal and anal cancers. GI cancers are the most common tumour type
[1]
encountered worldwide and represent the leading cause of cancer-related mortality . The only potentially
curative strategy for GI cancers is surgery; however the majority of GI cancers are unresectable at diagnosis.
Systemic or palliative treatments such as chemotherapy, radiotherapy, monoclonal antibody (mAb)
therapy or combination therapies have greatly improved survival rates in the last decade; however, the

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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