Timothy R. Gershon

Abstract Netrin-1 signaling is an essential prototypical neuronal guidance mechanism during embryonic development that also regulates tumor cell survival in a variety of adult cancer entities. In line with these data, a monoclonal netrin-1 blocking antibody (anti-netrin-1 mAb/NP137) has been preclinically developed and netrin-1 blockade has recently been investigated in phase 1 and 2 clinical trials in several adult cancers.

Abstract OLIG2-expressing tumor stem cells have been shown to drive recurrence in Sonic Hedgehog (SHH)-subgroup medulloblastoma (MB) and patients urgently need specific therapies to target this tumor cell population. Here, we investigate the therapeutic potential of the brain-penetrant orally bioavailable, OLIG2 inhibitor CT-179, using SHH-MB explant organoids, PDX and GEM SHH-MB models.

Commentary Video November 23, 2024 Author(s): Timothy Gershon, MD, PhD, discusses an analysis of patients with NF1-PN who achieved deep responses with mirdametinib in the phase 2b ReNeu study. “We didn’t find that there was a particular patient that we could identify who was more likely to be a strong responder. Male or female, young or old—none of these obvious characteristics helped us define who would be a strong responder.