Targeting MITF as a tyrosine-kinase-inhibitor-independent strategy for treating GIST

The source is a commentary discussing a novel, tyrosine-kinase-inhibitor-independent strategy for treating Gastrointestinal Stromal Tumors (GISTs) by targeting the transcription factor (TF) microphthalmia-associated transcription factor (MITF). Although GIST management currently relies on tyrosine kinase inhibitors (TKIs) like imatinib, the source highlights that resistance to these TKIs is a persistent problem, necessitating new approaches. The authors focus on a recent study by Guerrero et al. that demonstrated the small molecule inhibitor ML329 effectively suppresses the survival of both TKI-sensitive and TKI-resistant GIST models by targeting MITF, suggesting it is a key vulnerability in this cancer type. This research establishes MITF as a clinically actionable target and broadly explores how therapeutic strategies are evolving to overcome the historical challenge of targeting transcription factors in oncology.