Yebra, Mayra; Bhargava, Shruti; Kumar, Avi; Burgoyne, Adam M.; Tang, Chih-Min; Yoon, Hyunho; Banerjee, Sudeep; Aguilera, Joseph; Cordes, Thekla; Sheth, Vipul; Noh, Sangkyu; Ustoy, Rowan; Li, Sam; Advani, Sunil J.; Corless, Christopher L.; Heinrich, Michael C.; Kurzrock, Razelle; Lippman, Scott M.; Fanta, Paul T.; Harismendy, Olivier; Metallo, Christian; Sicklick, Jason K. published the artcile< Establishment of patient-derived succinate dehydrogenase-deficient gastrointestinal stromal tumor models for predicting therapeutic response>, Product Details of C19H34O2, the main research area is temozolomide anticancer succinate dehydrogenase gastrointestinal stromal tumor.
Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract, with mutant succinate dehydrogenase (SDH) subunits (A-D) comprising less than 7.5% (i.e., 150-200/yr) of new cases annually in the United States. Contrary to GISTs harboring KIT or PDGFRA mutations, SDH-mutant GISTs affect adolescents/young adults, often metastasize, and are frequently resistant to tyrosine kinase inhibitors (TKI). Lack of human models for any SDH-mutant tumors, including GIST, has limited mol. characterization and drug discovery. Exptl. Design: We describe methods for establishing novel patient-derived SDH-mutant (mSDH) GIST models and interrogated the efficacy of temozolomide on these tumor models in vitro and in clin. trials of patients with mSDH GIST. Mol. and metabolic characterization of our patient-derived mSDH GIST models revealed that these models recapitulate the transcriptional and metabolic hallmarks of parent tumors and SDH deficiency. We further demonstrate that temozolomide elicits DNA damage and apoptosis in our mSDH GIST models. Translating our in vitro discovery to the clinic, a cohort of patients with SDH-mutant GIST treated with temozolomide (n = 5) demonstrated a 40% objective response rate and 100% disease control rate, suggesting that temozolomide represents a promising therapy for this subset of GIST. We report the first methods to establish patient-derived mSDH tumor models, which can be readily employed for understanding patient-specific tumor biol. and treatment strategies. We also demonstrate that temozolomide is effective in patients with mSDH GIST who are refractory to existing chemotherapeutic drugs (namely, TKIs) in clinic for GISTs, bringing a promising treatment option for these patients to clinic.
Clinical Cancer Research published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (SDH). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Product Details of C19H34O2.
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