Open Access

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

  • Authors:
    • Alessandra Maleddu
    • Maria A. Pantaleo
    • Margherita Nannini
    • Monica Di Battista
    • Maristella Saponara
    • Cristian Lolli
    • Guido Biasco
  • View Affiliations

  • Published online on: June 1, 2009     https://doi.org/10.3892/or_00000361
  • Pages:1359-1366
0

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.

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June 2009
Volume 21 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Maleddu, A., Pantaleo, M.A., Nannini, M., Di Battista, M., Saponara, M., Lolli, C., & Biasco, G. (2009). Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review). Oncology Reports, 21, 1359-1366. https://doi.org/10.3892/or_00000361
MLA
Maleddu, A., Pantaleo, M. A., Nannini, M., Di Battista, M., Saponara, M., Lolli, C., Biasco, G."Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review)". Oncology Reports 21.6 (2009): 1359-1366.
Chicago
Maleddu, A., Pantaleo, M. A., Nannini, M., Di Battista, M., Saponara, M., Lolli, C., Biasco, G."Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review)". Oncology Reports 21, no. 6 (2009): 1359-1366. https://doi.org/10.3892/or_00000361