Clinical trial tests drug for tumors associated with Krebs-cycle dysfunction


The Krebs cycle is part of the complex process where cells turn food into energy. One of the elements of the Krebs cycle is succinate dehydrogenase (SDH). Loss of SDH activity in cells has been linked to tumor formation in wild-type gastrointestinal stromal tumors (GIST), pheochromocytoma, paragangliomas and a subtype of renal cell carcinoma. “Wild-type” means lacking a mutation in either of the two genes that usually play a role in GIST, pheochromocytoma is a hormone-secreting tumor of the adrenal glands, paragangliomas are rare tumors in peripheral nerve cells, and renal cell carcinoma is a type of kidney cancer. Guadacitabine represents a new strategy for attacking this biochemically related and difficult-to-treat group of tumors.

John Glod, M.D., Ph.D., of the Pediatric Oncology Branch, is leading a study of guadecitabine treatment for these diseases. Guadecitabine is designed to inhibit the growth of rapidly dividing tumor cells by modulating their DNA and may also make the cells more sensitive to chemotherapy or immunotherapy. For more information about this trial, please visit: https://ccr.cancer.gov/Pediatric-Oncology-Branch/john-w-glod.

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Summary Posted: 08/2017