Therapeutics: R-Spondin 1 (RSPO1); RSPO2; RSPO3

Patient sample and mouse studies suggest inhibiting RSPO1, RSPO2 or RSPO3 could help treat cancers. In primary tumor patient samples, RSPO1 was highly expressed in ovarian tumors, RSPO2 was highly expressed in lung and colorectal tumors, and RSPO3 was highly expressed in ovarian and lung tumors. In patient-derived xenograft mouse models of ovarian cancer, an anti-RSPO1 antibody plus the generic chemotherapy paclitaxel decreased tumor growth compared with either agent alone. In patient-derived xenograft mouse models of colorectal cancer, an anti-RSPO2 antibody plus irinotecan decreased tumor growth. In patient-derived xenograft mouse models of ovarian or lung cancer, an anti-RSPO3 antibody plus paclitaxel or irinotecan decreased tumor growth. Next steps could include testing the anti-RSPO mAbs in animal models of chemotherapy-resistant cancer.

OncoMed Pharmaceuticals Inc. has OMP-131R10, a mAb targeting RSPO3, in Phase I testing to treat colorectal cancer and solid tumors. ...