Reprogramming Pancreatic Cancer
Pamela Itkin-Ansari, Ph.D.
The Itkin-Ansari lab recently made the discovery that a single gene can halt pancreatic cancer tumor growth in animals and reprogram the cells back to their original identity. The results are especially exciting because a reprogramming approach has changed a once lethal leukemia, APL, into a completely treatable disease. Our goal is to develop a reprogramming strategy for pancreatic cancer.
1 Lee SH, Hao E, Kiselyuk A, Shapiro J, Shields D, Lowy A, Levine F, Itkin-Ansari P. 2011. The Id3/E47 axis mediates cell cycle control in human pancreatic ducts and adenocarcinoma. Molecular Cancer Research; 9(6):782-790 (cover feature) PMCID: 3954712.
2 Kim S, Lahmy R, Riha C, Yang C, Jakubison BL, van Niekerk J, Staub C, Wu Y, Gates K, Dong DS, Konieczny SF, Itkin-Ansari P. 2015 The Basic Helix-Loop-Helix Transcription Factor E47 Reprograms Human Pancreatic Cancer Cells to a Quiescent Acinar State With Reduced Tumorigenic Potential. Pancreas. Jul;44(5):718-27. doi: 10.1097 PMCID:4464938.
To exploit the previously unrecognized plasticity of pancreatic cancer cells and translate our findings to the clinic we must identify a drug, or drugs, that will accomplish what we did genetically in mice. Therefore, we developed a platform to screen thousands drugs for potential reprogramming capability in PDA. The manuscript describing development of the screen is now in press.
3 Villiarino R, Signaevskaia, L, van Niekerk J , Medal R, Kim H, Lahmy R, Kathleen Scully K, Pinkerton A, Kim SW, Lowy A, Itkin-Ansari P. 2017. A screen for inducers of bHLH activity identifies pitavastatin as a regulator of p21, Rb phosphorylation and E2F target gene expression in pancreatic cancer. Oncotarget in press
From an early test of the screen using known drugs, we identified 3 that impact pathways of interest. In follow up studies we will determine the mechanisms and degree to which these compounds act on pancreatic cancer cells, singly and in combinations. In parallel, the lab is studying key elements of the reprogramming process in order to identify new drug targets.