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Current Colorectal Cancer Reports

, Volume 9, Issue 4, pp 331–340 | Cite as

Role of Apoptosis in Colon Cancer Biology, Therapy, and Prevention

  • Lin Zhang
  • Jian Yu
Molecular Biology (S Anant, Section Editor)

Abstract

Deregulation of apoptosis is a hallmark of human cancer and contributes to therapeutic resistance. Recent advances in cancer genomics have revealed a myriad of alterations in key pathways that directly or indirectly increase tumor cell survival. This review outlines the pathways of apoptosis in mammalian cells, and highlights the common alterations of apoptosis regulators found in colon cancer, the role of apoptosis, and underlying mechanisms in colon cancer treatment and prevention, including recent advances in investigational agents, such as kinase inhibitors, proteasome inhibitors, heat shock protein 90 inhibitors, BH3 mimetics, tumor necrosis factor related apoptosis-inducing ligand, and inhibitor of apoptosis protein antagonists. The topics also include novel concepts as well as opportunities and challenges for drug discovery and combination therapy by exploring cancer-specific genetic defects, and therefore selective induction of apoptosis in cancer cells. Although the emphasis is on colon cancer, the main theme and many of the aspects are applicable to other solid tumors.

Keywords

Apoptosis Colon cancer Bcl-2 family BH3-only protein Mitochondria Death receptor Tumor necrosis factor related apoptosis-inducing ligand Epidermal growth factor receptor KRAS B-Raf c-Myc Phosphatidylinositol 3-kinase Inhibitor of apoptosis proteins Targeted therapies Sorafenib Regorafenib Vemurafenib Protesome inhibitors Heat shock protein 90 inhibitors Autophagy Necrosis BH3 mimetics SMAC mimetics Nonsteroidal anti-inflammatory drugs Synthetic lethality 

Notes

Acknowledgments

Research in the authors’ laboratories is supported by National Institutes of Health grants CA106348, CA121105, and CA172136 and the V Foundation for Cancer Research (L.Z.), and American Cancer Society grant RSG-10-124-10-CCE and National Institutes of Health grants CA129829 and U01DK085570 (J.Y.).

Compliance with Ethics Guidelines

Conflict of Interest

Lin Zhang has received compensation for US patents 5,695,937, 5,866,330, 6,383,743, 6,746,845, and 6,333,152, and has received royalties from Johns Hopkins University for the preparation of genetically engineered cells.

Jian Yu has received compensation for US patent WO 02/064790, and has received royalties from Johns Hopkins University for the preparation of genetically engineered cells.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.University of Pittsburgh Cancer InstitutePittsburghUSA
  2. 2.Department of Pharmacology & Chemical BiologyPittsburghUSA
  3. 3.Department of PathologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Hillman Cancer Center Research PavilionPittsburghUSA

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