Cancer

Mouse studies suggest combining LGR5, LRP6 or PORCN inhibitors with Erivedge vismodegib could help treat BCC. In two mouse models of BCC, diphtheria toxin-mediated depletion of LGR5 decreased tumor burden compared with no treatment. In one of the models, the oral PORCN inhibitor LGK974 decreased tumor burden. In a mouse model of residual BCC following treatment with Erivedge, Erivedge plus LGR5 depletion or LGK974 decreased tumor burden compared with Erivedge alone. Also in the residual BCC model following treatment with Erivedge, an anti-LRP6 mAb plus Erivedge decreased the number of residual tumor nests and increased time to tumor regrowth compared with Erivedge alone. Next steps could include identifying and testing small molecule inhibitors of LGR5 and LRP6.

The Genentech Inc. unit of Roche, Chugai Pharmaceutical Co. Ltd. and Curis Inc. market Erivedge for BCC and have the compound in Phase II testing for acute myelogenous leukemia (AML) and pancreatic cancer. Genentech and Curis also have the product in Phase I testing for myeloproliferative disorder...