Optimizing Targeted Therapy for Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia
Mené en Chine sur 189 patients pédiatriques atteints d'une leucémie lymphoblastique aiguë positive pour le chromosome Philadelphie (âge médian : 7,8 ans ; durée médiane de suivi : jusqu'à 26 mois), cet essai randomisé multicentrique de phase III compare l'efficacité, du point de vue de la survie sans progression, d'une chimiothérapie intensive à base de dasatinib (inhibiteur de Abl-tyrosine kinase de deuxième génération) par rapport au mésylate d'imatinib (inhibiteur de première génération)
In 1996, Druker and colleagues published the initial report on the inhibitory effects of a compound later named imatinib, a BCR-ABL inhibitor that reduced proliferation of BCR-ABL–positive chronic myeloid leukemia (CML) cells in vitro. The concluding paragraph of their report captures the compelling promise of targeted anticancer therapy: “This compound serves as an example of a drug that was rationally designed to inhibit the function of a specific protein when the protein’s function was known to be involved in the pathogenesis of a specific disease state. It is hoped that by directing therapy toward the underlying disease mechanism, this will result in more effective and less toxic therapies.”(p565)
JAMA Oncology , éditorial, 2019