Vol 5, No 6 (2009)
Review paper
Published online: 2010-03-01

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Clinical and molecular aspects of gastrointestinal stromal tumors

Piotr Rutkowski, Zbigniew I. Nowecki
Onkol. Prak. Klin 2009;5(6):219-228.

Abstract

Gastrointestinal stromal tumors (GIST) comprise the entity of the most common mesenchymal neoplasms of gastrointestinal tract. Advances in knowledge of molecular mechanisms of GISTs led to development of therapy methods, which are the model of molecular targeted therapy in oncology. Introduction to clinical practice imatinib mesylate [inhibiting kinases - KIT/PDGFRA (platelet-derived growth factor receptor-α)] revolutionized therapy of advanced (inoperable and/or metastatic) GISTs. Imatinib has been recently registered also for adjuvant therapy after resection of primary GIST with significant risk of recurrence. In majority of patients treated with imatinib the resistance to this therapy developes. Scientific advances allowed for partial explanation of mechanisms of disease progression during imatinib therapy. The development of secondary mutations in KIT and/or PDGFRA genes is the most common mechanism of resistance. The only registered drug for second line therapy in GIST is sunitinib mesylate - multikinase inhibitor for e.g. KIT, PDGFRA/B, vascular endothelial growth factor receptors (VEGFR), FLT3, RET i colony stimulating factor 1 receptor (CSF-1R). Many other tyrosine kinase inhibitors and drugs acting on alternative signaling pathways (as heat shock protein 90, mTOR, insuline-like growth factor receptor) are currently investigated.

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