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The Oncologist, Vol. 11, No. 4, 342-357, April 2006; doi:10.1634/theoncologist.11-4-342
© 2006 AlphaMed Press

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Immunotherapy, Monoclonals, and Vaccines

Chemotherapeutic Approaches for Targeting Cell Death Pathways

M. Stacey Riccia, Wei-Xing Zongb

a National Cancer Institute and Food and Drug Administration Interagency Oncology Task Force, Bethesda, Maryland, USA; b Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA

Key Words. Chemotherapy • Apoptosis • Necrosis • Autophagy • Senescence • Mitotic catastrophe

Correspondence: Wei-Xing Zong, Ph.D., Department of Molecular Genetics and Microbiology, Stony Brook University, 128 Life Sciences Building, Stony Brook, New York 11794-5222, USA. Telephone: 631-632-4104; Fax: 631-632-9797; e-mail: wzong{at}notes.cc.sunysb.edu

For several decades, apoptosis has taken center stage as the principal mechanism of programmed cell death in mammalian tissues. It also has been increasingly noted that conventional chemotherapeutic agents not only elicit apoptosis but other forms of nonapoptotic death such as necrosis, autophagy, mitotic catastrophe, and senescence. This review presents background on the signaling pathways involved in the different cell death outcomes. A re-examination of what we know about chemotherapy-induced death is vitally important in light of new understanding of nonapoptotic cell death signaling pathways. If we can precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, perhaps we can succeed in more effective and less toxic chemotherapeutic regimens.




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