Fibroblast growth factor receptors as treatment targets in clinical oncology
Cet article passe en revue les études sur les inhibiteurs des facteurs de croissance des fibroblastes puis présente les principales stratégies susceptibles d'améliorer l'efficacité de ces traitements et d'éviter la survenue d'une résistance thérapeutique
FGFRs are receptor tyrosine kinases with a role in several biological processes, such as the regulation of development and tissue repair. However, alterations in FGFRs 1–4, such as amplifications, fusions and mutations, as well as aberrant epigenetic or transcriptional regulation and changes in tumour–stromal interactions in the tumour microenvironment, can lead to the development and/or progression of cancer. Similar to other kinase alterations, such alterations are targetable using small molecules or antibodies, and the benefits of FGFR inhibitors have been demonstrated in clinical trials involving subsets of patients with solid tumours harbouring FGFR alterations. However, the response rates in patients with FGFR alterations were relatively low, and responses in patients without detectable FGFR alterations were also observed. In this Review, the author describes the clinical experience with FGFR inhibitors to date, and highlights key aspects that might lead to improved response rates and/or the avoidance of acquired resistance, including the selection of patients who are most likely to benefit from treatment, and the use of FGFR inhibitors in combination regimens with other agents.
Nature Reviews Clinical Oncology , résumé, 2018