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Advances in targeted and immunobased therapies for colorectal cancer in the genomic era

Authors Seow H, Yip WK, Fifis T

Received 25 August 2015

Accepted for publication 22 January 2016

Published 31 March 2016 Volume 2016:9 Pages 1899—1920


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Narasimha Reddy Parine

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati

Heng Fong Seow,1 Wai Kien Yip,1 Theodora Fifis2

1Immunology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 2Department of Surgery, University of Melbourne, Melbourne, Australia

Abstract: Targeted therapies require information on specific defective signaling pathways or mutations. Advances in genomic technologies and cell biology have led to identification of new therapeutic targets associated with signal-transduction pathways. Survival times of patients with colorectal cancer (CRC) can be extended with combinations of conventional cytotoxic agents and targeted therapies. Targeting EGFR- and VEGFR-signaling systems has been the major focus for treatment of metastatic CRC. However, there are still limitations in their clinical application, and new and better drug combinations are needed. This review provides information on EGFR and VEGF inhibitors, new therapeutic agents in the pipeline targeting EGFR and VEGFR pathways, and those targeting other signal-transduction pathways, such as MET, IGF1R, MEK, PI3K, Wnt, Notch, Hedgehog, and death-receptor signaling pathways for treatment of metastatic CRC. Additionally, multitargeted approaches in combination therapies targeting negative-feedback loops, compensatory networks, and cross talk between pathways are highlighted. Then, immunobased strategies to enhance antitumor immunity using specific monoclonal antibodies, such as the immune-checkpoint inhibitors anti-CTLA4 and anti-PD1, as well as the challenges that need to be overcome for increased efficacy of targeted therapies, including drug resistance, predictive markers of response, tumor subtypes, and cancer stem cells, are covered. The review concludes with a brief insight into the applications of next-generation sequencing, expression profiling for tumor subtyping, and the exciting progress made in in silico predictive analysis in the development of a prescription strategy for cancer therapy.

Keywords: targeted therapies, colorectal cancer, signaling pathways, immune cells, personalized medicine

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