Targeting the Bcl-2

Mehul R. Patel, Aisha Masood, Priya S. Patel, Asher A Chanan Khan

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Members of the Bcl-2 family of proteins are critical components in regulating the intrinsic apoptotic pathway. Bcl-2 protein overexpression is associated with drug resistance and poor clinical outcome in cancer patients. Preclinical and clinical evaluations demonstrate that downregulation of Bcl-2 restores the intrinsic apoptotic pathways with antitumor effects. Thus, Bcl-2 is aggressively pursued as a therapeutic target in cancer with several new drugs undergoing clinical investigations. In this manuscript, we will review clinical information on some of the novel compounds specifically designed to target the Bcl-2 gene product(s). Extensive clinical evaluations using a Bcl-2-specific antisense have resulted in an overall disappointing experience. But new small molecule inhibitors of the Bcl-2 hold promise with high target affinity, ease of administration and improved toxicity profile. Early stage clinical trials of these agents are revealing promising results alone as well as in combination with existing anticancer therapeutics. Encouraging results from some of these clinical investigations are summarized in this review. Downregulation of Bcl-2 and restoration of a critical apoptotic pathway in cancer cells remains an important strategy. Novel Bcl-2 inhibitors have started to deliver the therapeutic promise of this target-specific quest.

Original languageEnglish (US)
Pages (from-to)516-523
Number of pages8
JournalCurrent Opinion in Oncology
Volume21
Issue number6
DOIs
StatePublished - Nov 2009
Externally publishedYes

Fingerprint

Down-Regulation
bcl-2 Genes
Neoplasms
Critical Pathways
Drug Resistance
Proteins
Therapeutics
Clinical Trials
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Bcl-2
  • Small molecule inhibitors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Targeting the Bcl-2. / Patel, Mehul R.; Masood, Aisha; Patel, Priya S.; Chanan Khan, Asher A.

In: Current Opinion in Oncology, Vol. 21, No. 6, 11.2009, p. 516-523.

Research output: Contribution to journalArticle

Patel, MR, Masood, A, Patel, PS & Chanan Khan, AA 2009, 'Targeting the Bcl-2', Current Opinion in Oncology, vol. 21, no. 6, pp. 516-523. https://doi.org/10.1097/CCO.0b013e328331a7a4
Patel, Mehul R. ; Masood, Aisha ; Patel, Priya S. ; Chanan Khan, Asher A. / Targeting the Bcl-2. In: Current Opinion in Oncology. 2009 ; Vol. 21, No. 6. pp. 516-523.
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