Presentation Time: 4:00-4:20
Home University: UNC-Chapel Hill
Research Mentor: Channing Der, Pharmacology
Program: CSF
Research Title: Validating gene targets of MYC transcriptional activity in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is the third deadliest cancer in the United States with a dismal 5-year survival rate of 10%. 97% of PDAC cases are driven by mutations in the KRAS oncogene, a GTPase that regulates a myriad of signaling cascades responsible for promoting cell growth, proliferation, and metabolism. When mutated, KRAS exists predominantly in its active, GTP-bound state, which allows it to constitutively signal to its downstream effectors and drive PDAC growth. One of the most notable signaling cascades activated by mutant KRAS is the RAF-MEK-ERK MAPK pathway, which has been the target of several small-molecule inhibitors. Unfortunately, resistance to these inhibitors arises quickly, possibly through KRAS-driven stabilization of the MYC transcription factor. MYC is a known oncogene in many cancer types, and its overexpression in PDAC has been well established. While effective pharmacologic inhibitors against members of the MAPK pathway exist, reliable MYC inhibitors have proven more elusive. A tool compound targeting MYC activity, 975, recently showed promising anti-tumor effects in prostate cancer mouse models, but has yet to be characterized in PDAC. Here, to gauge the effects of 975 on MYC activity in PDAC cells, target genes of MYC transcriptional activity were identified. Following acute suppression of MYC by siRNA knockdown, RNA-sequencing and subsequent qPCR analysis of PDAC cells indicated HSPD1, MYBBP1A, and CBL as candidate MYC-driven gene targets in PDAC.