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Trent Lab

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Investigator / Contact Person Jonathan C. Trent, M.D., Ph.D.

Research

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Most of these tumors harbor mutually exclusive gain of function mutations in the tyrosine kinase receptors KIT and PDGFR-ë±. Mutation causes the continuous activation of the tyrosine kinase receptor resulting in uncontrolled GIST cell proliferation, invasion, neoangiogenesis, and survival.   
Imatinib mesylate is a small molecule that inhibits the activation of KIT and PDGFR-ë± receptors and is the first line of treatment for patients with locally advanced and metastatic GIST. Patients with primary GIST may also be treated with preoperative or postoperative imatinib. Even though patients treated with imatinib have prolonged disease free and overall survival; recurrence, tumor progression and metastasis still occur in the majority of patients. Developing and validating new methods to predict recurrence, metastasis, or progression of disease prior to macroscopic detection by radiographic imaging will allow earlier treatment and could improve patient survival.
Circulating tumor DNA (ctDNA) is emerging as a biomarker for tumor progression and resistance to therapy. Detecting the frequency of circulating tumor DNA in patients could be an innovative noninvasive diagnostic tool and a monitoring system to assess cancer stage. Currently, new technologies give us the opportunity to be able to detect very low levels of ctDNA with precision and reproducibility. Analyzing ctDNA in plasma from GIST patients using highly sensitive technology and correlating this data with previous obtained clinical data could lead to earlier detection of tumor recurrence, metastasis, or progression of disease in GIST patients.