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Dr. Ghobrial is Assistant Professor of Medicine, Division of Hematology/Oncology, Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA.
Dr. Witzig is Professor of Medicine, Division of Hematology, Department of Internal Medicine, Mayo Medical School, Rochester, MN.
Dr. Adjei is Associate Professor of Oncology, Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN.
EMERGING TRENDS in BASIC SCIENCE The role of basic research as the foundation for clinical progress has never been more apparent than it is today. Research in molecular and cellular biology, epidemiology, immunology, radiation physics and radiobiology, information technology, and related fields begun decades ago is being translated into clinical practice of cancer prevention, early detection, and treatment at an accelerating rate. Although busy clinicians typically have limited time available for keeping up with basic research, remaining current with the key basic science principles can help them make decisions concerning the clinical fruits they bear.
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.
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