Class IA phosphoinositide 3-kinase isoforms and human tumorigenesis: Implications for cancer drug discovery and development

Susan Wee, Christoph Lengauer, Dmitri Wiederschain

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE OF REVIEW: The phosphoinositide 3-kinases are lipid kinases that are activated in response to external factors. They regulate a number of intracellular signaling pathways involved in cell motility, metabolism, survival, and growth. This review summarizes the current knowledge about specific contributions of Class IA phosphoinositide 3-kinases to tumorigenesis and presents a rationale for the development of isoform-specific inhibitors. RECENT FINDINGS: In the last decade, the Class IA phosphoinositide 3-kinases have gained considerable attention as drug targets for the treatment of cancer. Indeed, pan-phosphoinositide 3-kinase inhibitors are being evaluated in early phases of clinical trials for the treatment of multiple human malignancies. Accumulating evidence suggests that selectively targeting individual isoforms is also possible. However, the patient population that is most likely to benefit from such selective compounds remains to be elucidated. SUMMARY: Given the importance of the phosphoinositide 3-kinase pathway in the initiation and maintenance of human tumors, drugs that effectively target its constituents will be an invaluable addition to the arsenal of anticancer therapeutics. However, to fully capitalize on the central role of this pathway in malignancy, we must first fully understand the nuances of its multiple players.

Original languageEnglish (US)
Pages (from-to)77-82
Number of pages6
JournalCurrent Opinion in Oncology
Volume20
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Keywords

  • Cancer
  • Drug discovery
  • Phosphoinositide 3-kinase
  • PTEN

ASJC Scopus subject areas

  • Cancer Research

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