Two new studies were published in July and August 2021 focusing on SDH-deficient tumor models and how location can affect GIST tumor profiles and drug sensitivity. Establishment of Patient-derived Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumor models for predicting therapeutic response was published this week detailing an ongoing study of mutant SDH GIST tumor models focusing on molecular characterization and drug discovery. These patient-derived mSDH GIST models showed recapitulation of the transcriptional and metabolic hallmarks of parent tumors and SDH-deficiency. The study further demonstrated that temozolomide (ClinicalTrials.gov Identifier: NCT03556384), a drug currently in trial, elicits DNA damage and apoptosis in the models. They have successfully translated these discoveries to a cohort of SDH-mutant GIST patients and seen promising results.
“One of the major impediments to treating GIST is the misbelief that this disease is easily curable,” said Jason Sicklick, MD, professor of surgery in the Division of Surgical Oncology at University of California San Diego School of Medicine, and a GIST specialist. But in reality, we know this is not the case. Even patients with tumors predicted to be sensitive to certain drugs rarely have complete responses to therapy. There is more to the biology that needs to be discovered.”
Among the esteemed team of co-authors are Pediatric & SDH-Deficient Consortium & LRG Medical Advisory Board members Dr. Jason Sicklick, and Dr. Michael Heinrich of the OHSU Knight Cancer Institute, and a frequent speaker at LRG webinars on pathology Christopher Corless (OHSU).
UC San Diego Health published an article with more details about this study and Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity, published in July 2021.
In this earlier paper, published July 29, 2021, Sicklick and colleagues analyzed where GIST tumors arise in the stomach (the most common site) and their underlying mutations, suggesting that location may be an early clue to mutational type to guide optimal treatment.
Among the co-authors on this study are Dr. Sicklick, Dr. Heinrich, and Dr. Andrew Blakely from National Cancer Institute, who has participated in many LRG Virtual Tumor Boards and written articles for the LRG.
UC San Diego included many details about the scope of the studies and the funding sources in this article.