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Update on imatinib for gastrointestinal stromal tumors: duration of treatment

Authors Linch M, Claus J, Benson C

Received 30 April 2013

Accepted for publication 16 May 2013

Published 30 July 2013 Volume 2013:6 Pages 1011—1023


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Mark Linch,1,2 Jeroen Claus,2 Charlotte Benson1

1Sarcoma Unit, Royal Marsden Hospital, 2Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, London, United Kingdom

Abstract: Gastrointestinal stromal tumors (GISTs) are the most common sarcoma of the gastrointestinal tract, with transformation typically driven by activating mutations of c-KIT and less commonly platelet-derived growth factor receptor alpha (PDGFRA). Successful targeting of c-KIT and PDGFRA with imatinib, a tyrosine kinase inhibitor (TKI), has had a major impact in advanced GIST and as an adjuvant and neoadjuvant treatment. If treatment with imatinib fails, further lines of TKI therapy have a role, but disease response is usually only measured in months, so strategies to maximize the benefit from imatinib are paramount. Here, we provide an overview of the structure and signaling of c-KIT coupled with a review of the clinical trials of imatinib in GIST. In doing so, we make recommendations about the duration of imatinib therapy and suggest how best to utilize imatinib in order to improve patient outcomes in the future.

Keywords: adjuvant, c-KIT, mutations, resistance, treatment, gastrointestinal stromal tumors, imatinib

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