What is GIST?
Gastrointestinal stromal tumor (GIST) is a disease in which abnormal cells form in the tissues of the gastrointestinal tract: stomach, small intestine, and large intestine. GIST is the most common sarcoma of the gastrointestinal (GI) tract.
In approximately 5% of patients with GIST, defects in a gene called PDGFRα, known as D842V, lead to primary resistance to existing approved medications. Currently, there are no approved targeted therapy options for PDGFRα D842V mutant GIST. Prior Phase II clinical results suggest promising efficacy of crenolanib in patients with PDGFRα D842V mutant GIST.
Platelet derived growth factor receptors (PDGFRs) are tyrosine kinase receptors, that are involved in many normal cellular processes, including organogenesis, cell proliferation, angiogenesis, etc. These receptors come in two isoforms called PDGFRA and PDGFRB. PDGFR signaling can be altered by gene amplification or activating mutations. These aberrations in PDGFR have an incidence of about 30% in cancer. Tumor types for which PDGFR is altered in at least 10% of cases includes GIST, glioblastoma, lung, melanoma, bladder, prostate, colorectal and ovarian cancers.