Unleashing the Power of Inhibitors of Oncogenic Kinases Through BH3 Mimetics

Nat Rev Cancer. 2009 May;9(5):321-6. doi: 10.1038/nrc2615. Epub 2009 Apr 3.

Abstract

Therapeutic targeting of tumours on the basis of molecular analysis is a new paradigm for cancer treatment but has yet to fulfil expectations. For many solid tumours, targeted therapeutics, such as inhibitors of oncogenic kinase pathways, elicit predominantly disease-stabilizing, cytostatic responses, rather than tumour regression. Combining oncogenic kinase inhibitors with direct activators of the apoptosis machinery, such as the BH3 mimetic ABT-737, may unlock potent anti-tumour potential to produce durable clinical responses with less collateral damage.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Apoptosis / drug effects
  • Biphenyl Compounds / pharmacology*
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Humans
  • Nitrophenols / pharmacology*
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Sulfonamides / pharmacology*

Substances

  • ABT-737
  • Antineoplastic Agents
  • Biphenyl Compounds
  • Nitrophenols
  • Piperazines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Sulfonamides
  • Fusion Proteins, bcr-abl