Medulloblastoma is the most common malignant pediatric brain tumor, and despite advances in clinical approaches, currently available treatment regimens still fail children with MYC- and MYCN-driven tumors. Jonchere and colleagues conducted high throughput combination drug screens using an actively explored CDK4/6 inhibitor, ribociclib, as an anchor (the bedrock drug used in all combinations). Bromodomain and extra terminal (BET) and PI3K/mTOR inhibitors increased the ability of ribociclib to inhibit tumor cell proliferation in vitro and deplete target signaling genes in vivo. Highlighting the difficulty of translating in vitro findings in vivo, combination treatment did not significantly improve survival in tumor-bearing mice, preventing its translation to the clinic.
There is an unmet medical need in several cancer indications that express the tumor associated antigen 5T4. In this paper, Nelson and colleagues describe the development of a novel bispecific antibody that stimulates 4-1BB function when co-engaged with the 5T4 expressed on tumor cells....