Review Article Harnessing the cell death pathway for targeted cancer treatment

Introduction The balance between survival and death is of such importance that the cell spends consider-able energy maintaining it. Nowhere else is the maintenance of this balance more fraught with risk than in the cancer cell. The birth and death of a cancer cell hinges on the function of sev-eral ancient, highly conserved cell death path-ways; apoptosis, necrosis, and autophagy. For cells to generate tumors, there are often accom-panying defects in the progression of cell death that can eventually result in neoplasia. This is the basis for cancer therapies that attempt to rescind a cancer cell’s longevity, and has been one of the most important goals of research. The approach has been to target the cell death pathways, particularly apoptosis, to render a cancer cell once again sensitive to regulated cell death. To identify the best target for enhancing cell death in cancer cells, we must first understand the defects in the cell death pathways that gen-erate cancer cell tumorigenesis and treatment resistance. Many cancer therapies aim to in-duce cell death in order to curb tumor growth. However, the presence of genetic defects in cancer cells limits the clinical efficacy of these death-inducing agents. Therefore, more fo-cused individualized therapy is needed to ad-dress these defects to improve clinical out-come. Although much is known about apoptosis, other death pathways have only recently gained atten-tion as potential targets of therapy. Because defects in cell death pathways are nearly ubiqui-tous among cancers, targeting the cell death components can be used as a comprehensive treatment strategy for a broad range of cancers. However, understanding the differences be-tween the cell death pathway defects in each type of cancer can offer a more tailored ap-proach to choosing treatments to enhance cell death that is specific and effective. Am J Cancer Res 2011;1(1):43-61 www.ajcr.us /ISSN:2156-6976/ajcr0000002