chemotherapeutic approaches for targeting cell death pathways.docVIP

Chemotherapeutic Approaches for Targeting Cell Death Pathways 【关键词】nbsp; Chemotherapy,amp;#8226;,Apoptosis,amp;#8226;,Necrosis,amp;#8226;,Autophagy,amp;#8226;,Senescence,amp;#8226;,Mitotic,catastrophe 　　LEARNING OBJECTIVESnbsp; 　　After completing this course, the reader will be able to: 　　List the multiple cell death pathways that are activated in response to chemotherapeutic agents. 　　Identify signaling molecules involved and morphological changes that occur in the different types of cell death pathways. 　　Describe mechanisms targeted by novel chemotherapeutic agents. 　　ABSTRACTnbsp; nbsp; 　　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. 　　INTRODUCTIONnbsp; nbsp; 　　Strategically targeted cancer therapies are emerging from enormous efforts spent investigating basic signaling mechanisms involved in cell growth and cell death pathways. Many of the novel small molecules and biological agents being developed target pathways involved in apoptosis. Uncovering the molecular events that control and mediate apoptotic death has been fascinating and encouraged by the wealth of reagents and assays that offer specificity in detection. Examination of other modes of cell death has lagged behind, in part bec