Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review).

Abstract:

:Treatment of patients affected by advanced or inoperable GIST was revolutionized by the use of the tyrosine kinase inhibitors. Despite the fact that most patients have a good durable response of disease, they develop a resistance to treatments after a median time of 24 months. The acquired resistance is an emerging aspect in medical oncology especially in the era of target therapies. The aim of this review is to report all known mechanisms of secondary resistance to tyrosine kinase inhibitors and to highlight their clinical implications. In general, they may be divided in mechanisms related to the acquisition of new molecular abnormalities associated to KIT and PDGFRA receptor signalling pathway, such as the loss of KIT expression, the genomic amplification of KIT, the activation of an alternative downstream signalling pathways such as AKT/mTOR and the acquisition of new receptor mutations, and other mechanisms different to KIT/PDGFRA receptors. Future research perspectives on target therapy and early resistance evaluation are also discussed.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Maleddu A,Pantaleo MA,Nannini M,Di Battista M,Saponara M,Lolli C,Biasco G

doi

10.3892/or_00000361

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

1359-66

issue

6

eissn

1021-335X

issn

1791-2431

journal_volume

21

pub_type

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