Targeting osteosarcoma
Menée sur des échantillons de tissu tumoral et de tissu sain prélevés sur 59 patients atteints d'un ostéosarcome, puis in vitro et in vivo, cette étude suggère l'intérêt d'une stratégie thérapeutique visant à inhiber la signalisation PI3K/mTOR
Small-molecule targeted therapies have significantly improved the treatment landscape for many cancers. When a patient’s tumor expresses the protein kinase BCR-ABL or the protein kinase BRAFV600E, or overexpresses the androgen receptor, we now know what to do: treat with the corresponding small molecule that targets the driver oncogene. However, in a so-called “orphan cancer” such as osteosarcoma (OS) with no known driver oncogenes, finding an effective targeted therapy is a tall order. In PNAS, Perry et al. (1) undertook this challenge by starting with state-of-the-art gene sequencing, following up with comparison to an OS mouse model, proceeding to uncover therapeutically tractable targets with a genome-wide reverse genetic screen, and finally validating the genetic hits with small-molecule drugs currently in clinical trials for various cancers. Perry et al.’s multifaceted approach identified the phosphatidylinositol 3-kinase/mammalian target of rapamycin (PI3K/mTOR) pathway as a potential new OS treatment target (1).
Proceedings of the National Academy of Sciences , commentaire, 2014