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

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)...

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Main Authors: Heng, Fong Seow, Wai, Kien Yip, Fifis, Theodora
Format: Article
Language:English
Published: Dove Medical Press 2016
Online Access:http://psasir.upm.edu.my/id/eprint/54981/1/Advances%20in%20targeted%20and%20immunobased%20therapies.pdf
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author Heng, Fong Seow
Wai, Kien Yip
Fifis, Theodora
author_facet Heng, Fong Seow
Wai, Kien Yip
Fifis, Theodora
author_sort Heng, Fong Seow
collection UPM
description 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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spelling upm.eprints-549812018-07-11T08:57:43Z http://psasir.upm.edu.my/id/eprint/54981/ Advances in targeted and immunobased therapies for colorectal cancer in the genomic era Heng, Fong Seow Wai, Kien Yip Fifis, Theodora 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. Dove Medical Press 2016-03-31 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/54981/1/Advances%20in%20targeted%20and%20immunobased%20therapies.pdf Heng, Fong Seow and Wai, Kien Yip and Fifis, Theodora (2016) Advances in targeted and immunobased therapies for colorectal cancer in the genomic era. OncoTargets and Therapy, 9. pp. 1899-1920. ISSN 1178-6930 10.2147/OTT.S95101
spellingShingle Heng, Fong Seow
Wai, Kien Yip
Fifis, Theodora
Advances in targeted and immunobased therapies for colorectal cancer in the genomic era
title Advances in targeted and immunobased therapies for colorectal cancer in the genomic era
title_full Advances in targeted and immunobased therapies for colorectal cancer in the genomic era
title_fullStr Advances in targeted and immunobased therapies for colorectal cancer in the genomic era
title_full_unstemmed Advances in targeted and immunobased therapies for colorectal cancer in the genomic era
title_short Advances in targeted and immunobased therapies for colorectal cancer in the genomic era
title_sort advances in targeted and immunobased therapies for colorectal cancer in the genomic era
url http://psasir.upm.edu.my/id/eprint/54981/1/Advances%20in%20targeted%20and%20immunobased%20therapies.pdf
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