Targeting Apoptosis to Overcome Chemotherapy Resistance

Excerpt

Chemotherapy resistance is a major limiting factor for the extensive use of chemotherapeutic drugs in cancer treatment. Despite the large number of newly discovered medications, treatment success rates are still unsatisfactory. Programmed cell death, called apoptosis, is one of the main tissue homeostasis mechanisms that balances cell survival and death. Apoptosis can be induced through extrinsic and intrinsic pathways or repressed by inhibitor proteins. During tumor progression, homeostasis between the anti-apoptotic and pro-apoptotic regulators is disturbed and shifted towards survival through various escape mechanisms. Dysregulation of apoptosis-regulatory mediators, particularly high levels of anti-apoptotic proteins, is one of the main mechanisms by which tumor cells acquire resistance to chemo- and radiotherapy. Therefore, it is important to restore apoptosis in the chemo- and radiotherapy-resistant tumor cells. In this chapter, we summarize general chemotherapy resistance mechanisms, discuss the role of extrinsic and intrinsic pathways in chemoresistance, and review the current experimental strategies to overcome chemotherapy resistance targeting the apoptotic pathways.