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

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.

journal_name

Curr Opin Oncol

authors

Wee S,Lengauer C,Wiederschain D

doi

10.1097/CCO.0b013e3282f3111e

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

77-82

issue

1

eissn

1040-8746

issn

1531-703X

pii

00001622-200801000-00012

journal_volume

20

pub_type

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