Clinical impact of primary and secondary KIT mutations on the efficacy of molecular-targeted therapies in gastrointestinal stromal tumors
Secondary KIT mutations play a crucial role in imatinib resistance and the efficacy of second- and third-line therapies.
Gastrointestinal stromal tumors (GISTs) are commonly driven by primary mutations in KIT or PDGFRA. Imatinib is the first‑line therapy for GISTs. However, secondary mutations frequently emerge during imatinib treatment, contributing to resistance and influencing the efficacy of subsequent tyrosine kinase inhibitors, such as sunitinib and regorafenib. This study aimed to investigate the clinical relevance of both primary and secondary KIT mutations in treating and prognosing unresectable or recurrent GISTs.
The study demonstrates that the location of secondary KIT mutations predicts response to second‑line (sunitinib) and third‑line (regorafenib) therapies, suggesting that genetic profiling at initial diagnosis and upon resistance can guide personalized treatment strategies for patients with unresectable or recurrent GISTs.
Bizonyítékszint: Klinikai vizsgálat. Formális klinikai vizsgálati eredmény.
Kapcsolódó jelek
- A case report of advanced small intestinal stromal tumor with KIT gene mutation and BRCA2 deletion after multi-line treatments
- Review of Genomic Testing and SDH Deficiency in Gastrointestinal Stromal Tumors: Getting to the GIST
- Molecular Tailored Therapeutic Options for Advanced Gastrointestinal Stromal Tumors (GISTs): Current Practice and Future Perspectives
- Phase II study of neoadjuvant imatinib in large gastrointestinal stromal tumours of the stomach
- UK clinical practice guidelines for the management of gastrointestinal stromal tumours (GIST)