Combined surgical and molecular therapy: the gastrointestinal stromal tumor model.
OBJECTIVE
This review describes the pathologic and epidemiologic features of gastrointestinal stromal tumor (GIST) as well as the contemporary management of this tumor. The integration of surgery and treatment with targeted molecular agents in the treatment of GIST is highlighted.


BACKGROUND
GIST is the most common mesenchymal tumor of the gastrointestinal tract. Its cellular origin from the interstitial cell of Cajal and distinctness from smooth muscles tumors were only recently appreciated. The discovery of the centrality of KIT proto-oncogene mutations in the pathogenesis of this tumor, and the development of imatinib mesylate, a specific inhibitor of KIT tyrosine kinase function have revolutionized the treatment of GIST.


METHODS
We conducted a review of the English literature on GIST. The pathology, epidemiology, diagnosis, and treatment of this tumor are summarized with particular emphasis on recent developments in the field.


RESULTS
GIST is a rare tumor that usually arises from the stomach or small intestine. It is characterized by immunohistochemical staining for KIT. Treatment of primary localized tumors is surgical. The benefit of adjuvant treatment with the KIT tyrosine kinase inhibitor imatinib is the subject of investigation. The treatment of unresectable, recurrent, or metastatic GIST is primarily imatinib treatment. The integration of surgery or ablative modalities is often employed, particularly when all disease is amenable to gross resection or destruction, or when GIST becomes resistant to imatinib. Newer tyrosine kinase inhibitors, such as sunitinib are the subject of ongoing investigation.


CONCLUSIONS
The treatment paradigm for GIST has required the integration of surgery and molecular therapy and this will likely serve as a paradigm for the treatment of other solid tumors as targeted agents are developed.
Gold
Jason S
JS
Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Dematteo
Ronald P
RP
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000601:surgery*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000601:surgery*; D006801:Humans; D000068877:Imatinib Mesylate; D020360:Neoadjuvant Therapy; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011743:Pyrimidines / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001549:Benzamides; C000715470:MAS1 protein, human; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit