The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors

  • Alessandro Comandone | alessandro.comandone@h-gradenigo.it Division of Medical Oncology, Gradenigo Hospital, Torino, Italy.
  • Elisa Berno Oncology Unit, Ospedale Gradenigo, Turin and Piedmont Group for Sarcomas, Italy.
  • Simona Chiadò Cutin Oncology Unit, Ospedale Gradenigo, Turin and Piedmont Group for Sarcomas, Italy.
  • Antonella Boglione Oncology Unit, Ospedale Gradenigo, Turin and Piedmont Group for Sarcomas, Italy.

Abstract

Gastrointestinal stromal tumors (GISTs) are the commonest mesenchymal tumors of the gastroenteric tract, and are generally believed to originate from the neoplastic transformation of the interstitial cells of Cajal, the pacemaker structures of the stomach and intestine. Exon and genetic mutations (point/deletions) are fundamental for the development of GISTs: the constitutional characteristic of this neoplasm is the presence of the cell surface Kit receptor. Kit is the product of the proto-oncogene cKit, situated in chromosome 4. Ninety-eight percent of GISTs express mutated isoforms of Kit or of PDGFRA (Platelet growth factor receptor a). Kit mutation is the basic condition for autophosphorylation of tyrosine kinase residues in proteins. Autophosphorylation initiates pathogenetic processes in Cajal cells, toward a neoplastic transformation. Imatinib mesilate and, more recently, sunitinib are tyrosine kinase inhibitors, specific antagonists for Kit and PDGFRA, with good activity against GISTs. Most molecular and clinical data currently available concern imatinib. Exon mutations are strategic as prognostic and as predictive factors. In recent years, much evidence suggests that survival, response to therapy and resistance to imatinib are related to different mutations. In the near future, GIST patients will receive treatment differentiated by expressed Kit and PDGFRA mutations, thus truly individualized therapy.

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Published
2011-12-14
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Section
Reviews
Keywords:
Gastrointestinal stromal tumors - Kit and PDGFRA mutations - Clinical response - Resistance to tyrosine kinase inhibitors
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How to Cite
Comandone, A., Berno, E., Chiadò Cutin, S., & Boglione, A. (2011). The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors. Oncology Reviews, 2(2), 69-79. https://doi.org/10.4081/oncol.2008.112