Role of apoptotic response in cellular resistance to cytotoxic agents

Pharmacology & Therapeutics
F ZuninoF Arcamone

Abstract

The development of drug resistance is a major obstacle to effectiveness of chemotherapeutic treatment of human tumors with cytotoxic agents. Drug resistance is described as a multifactorial phenomenon, involving the expression of defense factors and/or detoxification mechanisms, alterations in drug-target interactions, and cellular response to specific cytotoxic lesions (in particular, DNA damage). Although the proposed mechanisms may contribute to the development of a variable degree of cellular resistance, it is possible that the cell response (i.e., DNA repair or apoptosis) following DNA damage plays a critical role in determining cellular chemosensitivity. The preclinical observations that tumor response to effective drug treatments is associated with induction of apoptosis support the possibility that a decreased susceptibility to apoptosis (apoptosis resistance) is relevant to clinical resistance. A number of molecular alterations associated with transformation and/or tumor progression may also be implicated in regulation of cell death pathways and in the development of drug resistance. There is evidence that the wild-type p53 is involved in cellular response to DNA damage, including cell cycle regulation, DNA repair, and...Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis