Cancer

Mouse and cell culture studies suggest inhibiting TACR1 or agonizing TRPV1 could help prevent pancreatic intraepithelial neoplasms (PanINs) from progressing to pancreatic ductal adenocarcinoma (PDAC). In a mouse model of PDAC, axon density was higher around PanIN lesions than in the pancreas of normal mice. In mouse PanIN organoids, co-culture with mouse sensory dorsal root ganglia (DRGs) increased proliferation of PanIN cells compared with co-culture with a mouse fibroblast cell line. In the organoids co-cultured with DRGs, two tool compounds that inhibit TACR1 decreased proliferation of the PanIN cells compared with vehicle. In a genetic mouse model of early stage PDAC, subcutaneous injection of resiniferatoxin (RTX) decreased progression from PanIN to PDAC. Next steps could testing the TACR1 inhibitors and RTX in additional models of early stage PDAC.

Sorrento Therapeutics Inc. has resiniferatoxin (RTX), a non-opiate TRPV1 agonist, in Phase I/II testing for chronic and severe refractory cancer pain...