Researchers at the Salk Institute have identified a “super-enhancer” that fuels the rapid growth of pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer.
Published in Nature Communications, the study also highlights the effectiveness of an experimental drug that halts the growth of pancreatic cancer by blocking this super-enhancer.
This groundbreaking research paves the way for new therapeutic approaches to treating one of the deadliest types of cancer.
The Role of Super-Enhancers
Super-enhancers are highly active regions of DNA that, when bound by proteins, significantly boost the expression of certain genes.
They can rapidly change the cellular state, leading to rapid growth or transformation. This study marks the first detailed examination of super-enhancers in pancreatic cancer.
hnRNPF Gene and Its Impact
The team analyzed 16 different human pancreatic cancer cell lines and discovered that the super-enhancer associated with the gene hnRNPF was far more active in cancer cells compared to healthy cells.
This super-enhancer sets off a cascade of events, increasing overall protein production, which fuels cancer growth.
Therapeutic Implications
Deleting the hnRNPF gene or the associated super-enhancer could slow down the growth of pancreatic cancer cells by over 80%.
An experimental drug targeting Prmt1, a protein affected by hnRNPF activation, effectively stopped the growth of isolated pancreatic tumors in lab experiments and in mice.
The researchers also found that the hnRNPF super-enhancer could be activated by Myc, a gene implicated in many types of cancer.
Since drugs directly targeting Myc have been challenging to develop, this discovery opens up a new avenue for therapy: disrupting the pathway turned on by the super-enhancer.
Clinical Relevance
The team tested cells from a human patient with pancreatic cancer, confirming that the hnRNPF super-enhancer was active, indicating its relevance for human cases and its potential use as a marker to monitor cancer progression.
Further research is needed to explore the therapeutic potential of drugs that target this super-enhancer or related pathways, paving the way for more effective treatment options for pancreatic cancer patients.
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“These results clearly demonstrate that this super-enhancer is relevant in humans and could even be used as a marker to monitor pancreatic cancer progression,” says Ronald Evans, the senior author of the study and director of Salk’s Gene Expression Laboratory.
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The research findings can be found in Nature Communications.
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