Scientists from Northwestern Medicine found a potential therapeutic target for the most common type of pancreatic cancer.
They found ISL2, a transcription factor, can act as a tumor suppressor in pancreatic ductal adenocarcinoma (PDA) tumors.
The research is published in Developmental Cell and was conducted by Mazhar Adli et al.
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 contain dense tissue and the cancer cells consistently reprogram their DNA transcription and metabolic functions to survive the tumor’s harsh microenvironment.
In the study, the team examined PDA tumor cell lines in mice to identify transcription factors and chromatin regulators that may be involved in PDA cell growth and proliferation.
They discovered the transcription factor islet-2 (ISL2) is silenced through DNA methylation in primary PDA tumors.
Notably, PDA tumors with high DNA methylation as ISL2 locus had more aggressive behavior, which was associated with poor patient survival.
A majority of the PDA tumor had higher levels of DNA methylation at ISL2 locus compared to normal tumor-adjacent tissue, suggesting that ISL2 is “silenced” in a majority of the pancreatic tumor.
The team found that increasing ISL2 expression with CRISPR-based epigenetic editing reduced PDA cell proliferation.
They also found that ISL2-depleted PDA cells may be sensitive to specific inhibitors.
Overall, the findings suggest that inhibiting pathways downstream of ISL2 epigenetic silencing may be a promising way to treat pancreatic cancer.
If you care about pancreatic cancer, please read studies about a new method to detect pancreatic cancer, and new treatment to fight pancreatic cancer.
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