Target Therapy in Unresectable or Metastatic Colorectal Cancer

Jae Hyun Kim; Seun Ja Park

doi:10.4166/kjg.2016.68.6.303

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Kim and Park: Target Therapy in Unresectable or Metastatic Colorectal Cancer

Review Article

Korean J Gastroenterol 2016;68(6):303-311.

Published online: 4 October 2016

DOI: https://doi.org/10.4166/kjg.2016.68.6.303

Target Therapy in Unresectable or Metastatic Colorectal Cancer

Jae Hyun Kim, Seun Ja Park

Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea

Correspondence to: Seun Ja Park, Department of Internal Medicine, Kosin University College of Medicine, 272 Gamcheon-ro, Seo-gu, Busan 49267, Korea. Tel: +82-51-990-5061, Fax: +82-51-990-5055, E-mail: parksj6406@daum.net

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Korea. Despite recent developments in the treatment of CRC, the median overall survival time in patients with metastatic CRC is less than 30 months. The biologic agents that target the epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have proven clinical benefits in the treatment of patient with metastatic CRC. Anti-EGFR agents, including cetuximab and panitumumab, as well as anti-VEGF agents, including bevacizumab, aflibercept, ramucirumab, and regorafenib have been shown to extend survival in combination with cytotoxic chemotherapy. In particular, the addition of anti-EGFR agents has demonstrated significant efficacy in patients with the RAS wild-type metastatic CRC. In the future, building a personalized treatment strategy, according to the clinical characteristics and biologic features of patients with unresectable or metastatic CRC, will be necessary. In this review, we summarized the mechanisms of target therapy, the results of main clinical trials, and the guideline of clinical practice in patients with unresectable or metastatic CRC.

CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2016. Korean Society of Gastroenterology.

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Fig. 1.

EGFR is a transmembrane glycoprotein receptor belonging to the ErbB family of tyrosine kinase proteins. If a ligand binds to the extracellular domain of epidermal growth factor receptor (EGFR), intracellular tyrosine kinase domain is activated by phosphorylation. Subsequently, several pathways, including PI3K/Akt, STAT, and RAS/RAF/MAPK are activated, and then cell signaling for proliferation, neoangiogenesis, and invasion and metastasis is initiated.

Fig. 2.

(A) VEGFR1 and VEGFR2 are expressed on the surface of blood endothelial cell, whereas VEGFR3 is mainly restricted to lymphatic endothelial cells. VEGF-A binds to both VEGFR1 and VEGFR2; VEGF-B and PLGF bind to VEGFR1; and VEGF-C and VEGF-D bind to VEGFR3. VEGFR2 is known to be a main mediator in the process of angiogenesis. (B) Bevacizumab binds to VEGF-A and inhibits the interaction with VEGFR-2 and subsequent angiogenesis. VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; PLGF, placental growth factor.

Fig. 3.

National Comprehensive Cancer Network guideline-recommended regimens as initial therapy for patients with unresectable or metastatic colorectal cancer.

Fig. 4.

(A) National Comprehensive Cancer Network (NCCN) guideline-recommended regimens as subsequent therapy for patients with unresectable or metastatic colorectal cancer (after first line therapy including bevacizumab). (B) NCCN guideline-recommended regimens as subsequent therapy for patients with unresectable or metastatic colorectal cancer (after first line therapy including cetuximab or panitumumab).

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