Lance Ostrom

TL;DR: By identifying a drug combination that delays or even combats development of resistance when used as a first-line treatment in clinical trials, these results could ultimately improve the lives of patients with medulloblastoma or other cancers that depend on Smo for their survival.

TL;DR: These studies provide insights into Wnt-induced LRP5/6 activation and show the potential utility of LRP6 antibodies in WNT-driven cancer.

TL;DR: In vivo, multivalent Nanobody molecules elicited superior anti-tumor activity compared to a conventional DR5 agonist antibody, including the ability to induce tumor regression in an insensitive patient-derived primary pancreatic tumor model, suggesting that multivalent DR5 Nanobodies may represent a significant new therapeutic modality for targeting death receptor signaling.

TL;DR: This study provides mechanistic evidence supporting the importance of linker choice for optimal antitumor activity and highlights CDH6 as an antigen for biotherapeutic development and demonstrates how an integrated pharmacology strategy that incorporates mechanistic pharmacodynamics and toxicology studies provides a rich dataset for optimizing the therapeutic format.

TL;DR: A selective Smo antagonist is developed, NVP-LDE225, which is orally bioavailable and potently inhibits Hh signaling in vitro and in vivo and suggests that Smo inhibitors can have a high impact on the treatment of this very aggressive cancer.