ENPP1 limits efficacy of radiation therapy in a murine pancreatic cancer model
oregon; portland; chiles
The aberrant regulation of replication in cancer cells and the effect of cytotoxic therapies can result in increased cGAMP production in tumors, resulting in STING activation and secretion of inflammatory cytokines. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) decreases cGAMP availability in the tumor, resulting in decreased STING pathway activation following cytotoxic therapy such as radiation therapy (RT). We hypothesize that removal of ENPP1 has potential to improve outcomes following cytotoxic therapy by optimizing STING pathway activation, and therefore enhancing anti-tumor immunity. We tested this in a murine pancreatic cell line with high expression of ENPP1. We found that removal of ENPP1 from this high expressing cancer line slowed tumor growth. Furthermore, we showed that RT treatment is more effective when ENPP1 is removed from this cell line. Therefore, ENPP1 inhibition has potential application alongside radiation therapy in patients to improve outcomes.
Baird, J; Alice, A; Ball, M; Kramer, G; Blair, T; Kaur, A; Gough, M; and Crittenden, M, "ENPP1 limits efficacy of radiation therapy in a murine pancreatic cancer model" (2022). Articles, Abstracts, and Reports. 6980.