Lessons from Structural Biology for Understanding Drug Resistance in Gastrointestinal Stromal Tumors (GIST).
Secondary and tertiary mutations across distinct regions of the kinase domain...
Gastrointestinal stromal tumors (GISTs) are primarily driven by activating mutations in the receptor tyrosine kinases KIT or PDGFRA. Targeted therapies have significantly improved patient outcomes; however, acquired drug resistance continues to limit long-term efficacy. Secondary and tertiary mutations across distinct regions of the kinase domain affect the conformational equilibrium or directly disrupt drug binding by alteration of critical residues. This perspective highlights key structural insights that elucidate the molecular basis of resistance and its interplay with kinase activation and TKI binding. A comprehensive understanding of these molecular alterations is crucial for guiding future therapeutic strategies to overcome resistance.
...
Evidence level: Feltételezés / hírjelzés. Nincs önálló tudományos bizonyíték.
Related signals
- Disproportionality analysis of adverse events associated with tyrosine kinase inhibitors in gastrointestinal stromal tumors in the FDA adverse event reporting system
- 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)