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

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    Author
    Seow, HF; Yip, WK; Fifis, T
    Date
    2016-01-01
    Source Title
    OncoTargets and Therapy
    Publisher
    DOVE MEDICAL PRESS LTD
    University of Melbourne Author/s
    Fifis, Theodora
    Affiliation
    Business & Economics
    Metadata
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    Document Type
    Journal Article
    Citations
    Seow, H. F., Yip, W. K. & Fifis, T. (2016). Advances in targeted and immunobased therapies for colorectal cancer in the genomic era. ONCOTARGETS AND THERAPY, 9, pp.1899-1920. https://doi.org/10.2147/OTT.S95101.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259279
    DOI
    10.2147/OTT.S95101
    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.

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