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Cancer Research Frontiers. 2015 Feb; 1(1): 37-48. doi: 10.17980/2015.37

Targeted Therapy for Gastrointestinal Stromal Tumor: Emerging concepts in oncogenetics and therapy sequencing

Lesly A. Dossett1, Mihaela Druta1, and Ricardo J. Gonzalez1[*]

1Sarcoma Department, Moffitt Cancer Center, Tampa, FL USA

 

*Corresponding author: Ricardo J. Gonzalez MD FACS, Chair, Sarcoma Department, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612. Email: ricardo.gonzalez@moffitt.org

Citation: Dossett LA, et al. Targeted Therapy for Gastrointestinal Stromal Tumor Emerging concepts in oncogenetics and therapy sequencing. Cancer Research Frontiers. 2015 Feb; 1(1): 37-48. doi: 10.17980/2015.37

Copyright: @ 2015 Dossett LA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Competing Interests: The authors declare that they have no competing interests.

Received Nov 26, 2014; Revised Jan 24, 2015; Accepted Feb 15, 2015; Published Feb 28, 2015.

 

 

Abstract

Gastrointestinal stromal tumor (GIST) is a relatively new tumor entity with the term first used 1983. GISTs were rarely diagnosed until after 2000 when Hiroto described the gain-of-function mutation in the c-kit proto-oncogene that was present in almost all GISTs. This discovery represented a major breakthrough in the classification, approach and treatment of these tumors. Shortly after this discovery, imatinib, a tyrosine kinase inhibitor initially developed as an agent for chronic mylogenous leukemia was found to inhibit KIT. The drug was demonstrated to be effective against metastatic GIST in a single patient with metastatic disease, and efficacy was confirmed in multiple subsequent phase II and phase III trials in the United States and Europe. Further understanding of tumor biology and oncogenetics, along with the application of targeted therapy, has revolutionized the treatment options and sequencing for patients with advanced GISTs. Available data suggest that mutational status has important implications for prognosis, recurrence, response to therapy and tyrosine kinase inhibitor resistance. A thorough understanding of mutational status in GIST is critical for appropriate selection of therapy, as well as understanding emerging areas for investigation.

Keywords: Cancer, sarcoma, gastrointestinal stromal tumor, gastric malignancy, GIST, tyrosine kinase, tyrosine kinase inhibition, c-kit, KIT, PDGFRA, imatinib, sunitinib, adjuvant therapy, neoadjuvant therapy, targeted therapy

 

 

 

 

 

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