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Topic: Reviews of Recent Advances in Research and Treatment for
Gastroenterological Malignancies

Trends in clinical use of targeted therapy for gastrointestinal cancers

Kojiro Eto, Masayuki Watanabe
Department of Gastroenterological Surgery, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
Correspondence to: Dr. Masayuki Watanabe, Department of Gastroenterological Surgery, Cancer Institute Hospital, 3-8-31 Ariake, Koto-ku,
Tokyo 135-8550, Japan. E-mail: masayuki.watanabe@jfcr.or.jp

ABSTRACT
Targeted drugs therapies that block the molecular pathways involved in the development and progression of gastro-intestinal (GI)
cancers have recently gained considerable attention. In addition to agents targeting vascular endothelial growth factor (VEGF),
epidermal growth factor receptor, the multi-kinase inhibitor, and regorafenib have also become available for the treatment
of metastatic colorectal cancer patients. Currently, trastuzumab, an antibody targeting human epidermal growth factor
receptor-2 (HER-2), in combination with cytotoxic drugs is considered as the standard treatment for patients with HER-2 positive
gastric cancer (GC). The effi cacy of ramucirumab, a human monoclonal antibody that inhibits VEGF from binding to its receptor
in GC, has also been recently demonstrated. At present, a great number of novel targeted drugs are in pre-clinical or clinical
studies. In this review, we summarize trends in the use of molecularly targeted drugs that have proven to be effective for treating
GI cancers, with a focus on emerging strategies for personalized treatment.
Key words: Gastro-intestinal tumors, molecular pathways, molecular targeted drug

Introduction therapies are needed. At present, a great number of novel
targeted drugs are in pre-clinical or clinical studies.
Many targeted drugs have been studied to target the
molecular pathways involved in the development The aim of this review is to provide a comprehensive
of gastro-intestinal (GI) cancers. Targeted drugs overview of the state of art, focusing on the new
therapies that block the molecular pathways involved emerging strategies in the personalized treatment of GI
in the development and progression of GI cancers cancers and discussing about the possible implications
have recently gained considerable attention. Several for GI cancers therapy.
molecular pathways were reported. Vascular endothelial
growth factor (VEGF) and epidermal growth factor The Main Pathways Targeted in Gastro-intestinal
receptor (EGFR), the multi-kinase inhibitor, regorafenib, Tumors
have also become available for the treatment of Many targeted drugs that block the molecular pathways
metastatic colorectal cancer (mCRC) patients. Currently, involved in the development and progression of GI
trastuzumab, an antibody targeting human epidermal tumors have been studied. Some of these agents are
growth factor receptor-2 (HER-2), in combination with most effi cacious in combination with conventional
cytotoxic drugs is considered to be the standard treatment chemotherapy regimens. The molecular targeted
for patients with HER-2 positive gastric cancer (GC). drugs that have been approved for the treatment of GI
The effi cacy of ramucirumab, a human monoclonal cancers are summarized in Table 1. We have reviewed
antibody (mAb) that inhibits VEGF from binding to its representative pathways that serve as targets in GI
receptor in GC, has also been recently demonstrated. cancers.
Although the above improvements have reduced GI Vascular endothelial growth factor pathway
cancers mortality in the past few decades, there is
suffi cient evidence suggesting that the majority of Angiogenesis is the process of new capillary
patients undergoing drug therapy will not benefi t and formation from pre-existing blood vessels, and it
will instead experience severe and even lethal adverse
drug events. Therefore, new and better molecular targeted This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
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How to cite this article: Eto K, Watanabe M. Trends in clinical use
of targeted therapy for gastrointestinal cancers. J Cancer Metastasis
DOI: Treat 2015;1:163-71.
10.4103/2394-4722.166997
Received: 04-08-2015; Accepted: 02-09-2015.

© 2015 Journal of Cancer Metastasis and Treatment ¦ Published by Wolters Kluwer - Medknow 163