Targeting osteosarcoma.

Abstract

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).