New therapeutic target for most common type of pancreatic ca
The study findings suggest ISL2, a transcription factor, can act as a tumor suppressor in pancreatic ductal adenocarcinoma (PDA) tumors and that its depletion reprograms PDA cells' transcriptional and metabolic states.

ISL2 status could be a precision medicine approach where we can check the tumor, look at ISL2 levels and then determine if these tumors are more dependent on lipid metabolism or if we should inhibit this pathway in these kind of tumors.

PDA has a poor survival rate—more than 80% of patients are diagnosed when the cancer is late-stage and the tumor no longer qualifies for surgical removal. Following diagnosis, average patient survival is typically four to six months. By nature, PDA tumors contains dense tissue and the cancer cells consistently reprogram their DNA transcription and metabolic functions to survive the tumor's harsh microenvironment.

The investigators found that increasing ISL2 expression with CRISPR-based epigenetic editing reduced PDA cell proliferation. Furthermore, they discovered that cells with low levels of ISL2 had a higher capacity to perform oxidative phosphorylation, a process in which the cell prefers oxidizing lipids and other metabolic products in the mitochondria instead of metabolizing glucose to sustain their bioenergetic needs. Overall, the findings suggest that inhibiting pathways downstream of ISL2 epigenetic silencing may be a promising therapeutic target.