Selected aspects of gastrointestinal stromal tumors management with tyrosine kinase inhibitors
Journal Title: OncoReview - Year 2012, Vol 2, Issue 1
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract that most frequently affect the stomach and small intestine. In the past these tumors may have been misclassified as leiomyosarcomas, leiomyomas or leiomyoblastomas. In the last decades the management of early and advanced GISTs has evolved substantially. Historically, surgery was the only effective therapeutic modality. There was no standard adjuvant therapy and almost all recurrent and advanced cases were deemed incurable because these tumors were unresponsive to conventional chemotherapy and radiotherapy. The majority of GISTs harbor mutations in genes encoding transmembrane receptors KIT or PDGFR-α that lead to constitutive activation of intracellular signaling, enhanced cell proliferation and consequently neoplastic transformation. Introduction of imatinib mesylate – a potent inhibitor of KIT and PDGFR-α – has dramatically changed GISTs management and profoundly affected the way we think of so-called targeted therapy of cancer. Nowadays, imatinib is a standard first-line therapy of advanced GISTs and adjuvant treatment of resected high-risk GISTs. Currently, sunitinib is the only registered second-line therapy after imatinib failure or intolerance, albeit many new drugs – mainly various tyrosine kinase inhibitors – are evaluated in controlled clinical trials. However, introduction of these new drugs into the clinic created also new controversies and uncertainties regarding assessment of treatment results, duration of therapy and dosing. Some of the aspects of tyrosine kinase inhibitors use in the management of GISTs along with a historical considerations have been addressed in our paper.
Authors and Affiliations
Bogumiła Czartoryska-Arłukowicz, Piotr Tokajuk, Marek Wojtukiewicz
Keywords
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