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Current clinical regulation of PI3K/PTEN/Akt/mTOR signalling in treatment of human cancer.

Abstract：

PURPOSE:PTEN is an essential tumour suppressor gene which encodes a phosphatase protein that antagonises the PI3K/Akt/mTOR antiapoptotic pathway. Impairment of this tumour suppressor pathway potentially becomes a causal factor for development of malignancies. This review aims to assess current understanding of mechanisms of dysfunction involving the PI3K/PTEN/Akt/mTOR pathway linked to tumorigenesis and evaluate the evidence for targeted therapy directed at this signalling axis. METHODS:Relevant articles in scientific databases were identified using a combination of search terms, including "malignancies", "targeted therapy", "PTEN", and "combination therapy". These databases included Medline, Embase, Cochrane Review, Pubmed, and Scopus. RESULTS:PI3K/PTEN expression is frequently deregulated in a majority of malignancies through genetic, epigenetic, and post-transcriptional modifications. This contributes to the upregulation of the PI3K/Akt/mTOR pathway which has been the focus of intense clinical studies. Targeted agents aimed at this pathway offer a novel treatment approach in a variety of haematologic malignancies and solid tumours. Compared to single-agent use, greater response rates were obtained in combination regimens, supporting further investigation of suitable drug combinations in a broad spectrum of malignancies. CONCLUSION:Activation of the PI3K/PTEN/Akt/mTOR pathway is implicated both in the pathogenesis of malignancies and development of resistance to anticancer therapies. Therefore, PI3K/Akt/mTOR inhibitors are a promising therapeutic option, in association with systemic cytotoxic and biological therapies, to enable sustained clinical outcomes in cancer treatment. Therapeutic strategies could be tailored according to appropriate biomarkers and patient-specific mutation profiles to maximise benefit of combination therapies.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Lim HJ,Crowe P,Yang JL

doi

10.1007/s00432-014-1803-3

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

671-89

issue

4

eissn

0171-5216

issn

1432-1335

journal_volume

141

pub_type

杂志文章,评审

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