UC San Diego

Advancements in therapeutics have seen mortality decrease for a variety of cancers. However, pancreatic cancer continues to develop resistance and progress to late-stage metastasis in patients. Research continues to investigate ways to counter these mechanisms set up by the tumor. Previous work done in the lab found characterized a therapeutic resistant population finding thousands of novel genes to be possible key regulators. Studies presented here focus on the novel pancreatic cancer regulator Prap1 and its function. Prap1 inhibition saw functional impact on the growth of pancreatic cancer across various murine and human in vitro and in vivo models. Characterization of this population identified DNA damage repair and ROS metabolism to be key functions downstream of Prap1. A possible feedback loop is activated in Prap1 inhibition as decreased ROS metabolism leads to higher amounts of DNA damage that can’t be repaired. These studies elucidate a unique role that Prap1 has within pancreatic cancer. Follow up studies were also performed on Celsr1, Celsr2, and Pear1in an inducible shRNA inhibition model on autochthonous in vivo tumors. Dox chow was found to be the most consistent and least taxing method on the mouse for induction of the vector. Studies here further compound that Celsr1 and Celsr2 are viable pancreatic cancer targets as shRNA positive cells were selected against in the tumor. These studies identify possible clinical targets in pancreatic cancer that can help overcome pancreatic cancer’s therapy resistance.