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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.

open access

Vol 5, No 6 (2009)
REVIEW ARTICLES
Published online: 2010-03-01

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.

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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Keywords

gastrointestinal stromal tumor; GIST; KIT; platelet-derived growth factor receptor-α VEGFRs; FMS-like tyrosine kinase-3; PDGFRA/B; rearranged during transfection; imatinib; sunitinib

About this article
Title

Clinical and molecular aspects of gastrointestinal stromal tumors

Journal

Oncology in Clinical Practice

Issue

Vol 5, No 6 (2009)

Article type

Review paper

Pages

219-228

Published online

2010-03-01

Bibliographic record

Onkol. Prak. Klin 2009;5(6):219-228.

Keywords

gastrointestinal stromal tumor
GIST
KIT
platelet-derived growth factor receptor-α VEGFRs
FMS-like tyrosine kinase-3
PDGFRA/B
rearranged during transfection
imatinib
sunitinib

Authors

Piotr Rutkowski
Zbigniew I. Nowecki

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