Targeting Apoptosis Pathways in Cancer Therapy


  • Dr. Irene M. Ghobrial MD,

    1. Ghobrial is Assistant Professor of Medicine, Division of Hematology/Oncology, Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA
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      1Dr. Ghobrial is supported in part by the Multiple Myeloma Research Foundation, the American Society of Clinical Oncology Young Investigator Award, the American Society of Hematology Scholar Award, and the Research Fund for Waldenstrom.

  • Dr. Thomas E. Witzig MD,

    1. Witzig is Professor of Medicine, Division of Hematology, Department of Internal Medicine, Mayo Medical School, Rochester, MN
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  • Dr. Alex A. Adjei MD, PhD

    1. Adjei is Associate Professor of Oncology, Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN
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Apoptosis, or programmed cell death, is a mechanism by which cells undergo death to control cell proliferation or in response to DNA damage. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy. These novel agents include those targeting the extrinsic pathway such as tumor necrosis factor-related apoptosis-inducing ligand receptor 1, and those targeting the intrinsic Bcl-2 family pathway such as antisense bcl-2 oligonucleotides. Many pathways and proteins control the apoptosis machinery. Examples include p53, the nuclear factor kappa B, the phosphatidylinositol 3 kinase pathway, and the ubiquitin/proteosome pathway. These can be targeted by specific modulators such as bortezomib, and mammalian target of rapamycin inhibitors such as CCI-779 and RAD 001. Because these pathways may be preferentially altered in tumor cells, there is potential for a selective effect in tumors sparing normal tissue. This article reviews the current understanding of the apoptotic pathways, including the extrinsic (cytoplasmic) and intrinsic (mitochondrial) pathways, and the agents being developed to target these pathways.