Anti-apoptotic mechanisms of drug resistance in cancer

Curr Cancer Drug Targets. 2009 May;9(3):307-19. doi: 10.2174/156800909788166547.


Resistance to chemotherapy is a major obstacle in the treatment of cancer. Despite the advent of new chemotherapies and molecular-targeted therapies, approximately 90% of patients with metastatic cancer succumb to their disease. Drug resistance, either acquired or intrinsic, often prevents tumour cells from undergoing sufficient levels of programmed cell death or apoptosis, resulting in cancer cell survival and treatment failure. In pre-clinical disease models, agents that target the apoptotic pathway have been shown to sensitize tumour cells to chemotherapy and radiotherapy. Such therapies include small molecule inhibitors and antisense strategies that inhibit the activity of anti-apoptotic proteins, or treatment with recombinant pro-apoptotic proteins or antibodies that can activate the apoptotic pathway. This review will discuss apoptosis and the mechanisms by which it can become dysregulated in human cancer. In addition, novel therapeutic strategies that target key components of the apoptotic machinery will be discussed.

Publication types

  • Review

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / drug effects
  • Apoptosis Regulatory Proteins / physiology
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / physiology*
  • Homeostasis
  • Humans
  • Inhibitor of Apoptosis Proteins / drug effects
  • Inhibitor of Apoptosis Proteins / physiology
  • Models, Biological
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Neoplasms / physiopathology
  • Receptors, Death Domain / physiology


  • Apoptosis Regulatory Proteins
  • Inhibitor of Apoptosis Proteins
  • Receptors, Death Domain