Therapeutics: CXC chemokine receptor 2 (CXCR2; IL8RB); programmed cell death 1 (PD-1; PDCD1; CD279)

Patient sample and mouse studies suggest inhibiting CXCR2 could help treat pancreatic ductal adenocarcinoma (PDAC). In patient samples, high levels of CXCR2 in neutrophils at the tumor borders correlated with disease progression and poor survival. In a mouse model of PDAC, systemic CXCR2 knockout decreased metastasis and increased T cell recruitment to the tumor compared with normal expression. Also in the model, Gemzar gemcitabine plus a peptide or small compound inhibitor of CXCR2 increased immune cell infiltration in tumors and survival and decreased metastasis compared with vehicle or any agent alone. In a mouse model of late-stage PDAC, the small molecule plus anti-PD-1 antibody increased survival compared with either agent alone. Next steps could include identifying and testing druggable CXCR2 inhibitors in other animal models of pancreatic cancer.

Eli Lilly and Co. markets Gemzar, a nucleoside analog that inhibits DNA synthesis, to treat breast cancer, pancreatic cancer and non-small cell lung cancer (NSCLC) and has the compound in Phase III testing to treat biliary and cervical cancers and Phase II testing to treat bladder cancer. ...