Inhibition of KIT Tyrosine Kinase Activity: Two Decades After the First Approval
Cet article passe en revue les connaissances acquises au cours des 20 dernières années qui ont suivi l'autorisation de l'imatinib, le premier inhibiteur de récepteurs à tyrosine kinase KIT
In 2002, we published a review in Journal of Clinical Oncology examining the potential of KIT inhibition to treat advanced cancer.1 At that time, imatinib was the first and only US Food and Drug Administration–approved kinase inhibitor and there were many unanswered questions (Table 1). Now, nearly 20 years later, there are five FDA-approved KIT-targeted kinase inhibitors, including imatinib. We have learned a great deal more about KIT and how mutations affect its function. We have also elucidated how specific secondary KIT mutations confer drug resistance in patients. This review will explore the journey of therapeutic KIT targeting that began with imatinib 20 years ago. We will discuss the basic research and clinical findings that informed the development of additional KIT inhibitors and how they were successfully integrated into patient care to combat resistance. We will make comparisons between the two malignancies that have been most significantly affected by KIT-targeted therapies, GI stromal tumor (GIST) and mast cell malignancies, to highlight the importance of genetic profiling in informing treatment success. Furthermore, we will discuss the lessons learned through the development of the five FDA-approved KIT targeted therapies (Table 2) and predictions for the future of the field.
Journal of Clinical Oncology , résumé, 2020