Gastrointestinal stromal tumors (GISTs).
OBJECTIVE
Gastrointestinal stromal tumors (GISTs) have recently been the subject of considerable clinical and experimental interest. This focus is based on the recognition that GISTs characteristically have uncontrolled activation of the KIT protein, a transmembrane tyrosine kinase receptor involved in cell survival, development, and proliferation. The clinical application of imatinib mesylate, a selective inhibitor of the KIT kinase activity, has provided a novel molecularly targeted therapy for these tumors. This review summarizes publications from the last year regarding these tumors.


RESULTS
Recent studies have focused on imaging, the identification of prognostic factors and molecular events, and the role of systemic therapy in the treatment of these tumors. Emerging data suggest that the combination of endoscopic ultrasound and fine-needle aspiration analysis for KIT expression may be useful in separating these lesions from other submucosal lesions of the gastrointestinal tract. The benefits and limitations of computed tomography and positron emission tomography in identifying, staging, and evaluating the response to therapy of these lesions have been more clearly defined. Although tumor size and the number of mitoses remain the best prognostic markers, several studies reported provocative data using other markers such as Ki-67, p53, and alterations in p16. Mutational analysis of the KIT oncoprotein continues to be the subject of considerable interest in relation to both prognosis and resistance to therapy. Finally, a series of new studies have confirmed the benefits and better defined the results of therapy with imatinib mesylate. There is increasing interest in expanding the role of this agent into the adjuvant setting and in combining such therapy with reoperation for responsive disease.


CONCLUSIONS
In the past year there have been significant developments in our understanding of GISTs and their response to therapy. Many questions remain unanswered and new issues have arisen as the benefits of imatinib mesylate therapy are revealed. There is considerable optimism that the targeted molecular approach being applied to the treatment of GISTs will serve as a model for the development of similar approaches to other more common tumors.
Saund
Mandeep S
MS
Department of Surgery, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Demetri
George D
GD
Ashley
Stanley W
SW