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Pancreatic cancers are among the most challenging and lethal types of tumors. For years, a comprehensive understanding of their growth dynamics and effective drug therapy have remained elusive. Now, Salk Institute's latest research presents a significant step forward in this direction.
Recently published in Nature Communications, Salk scientists elucidated the role of a certain "super-enhancer" in pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer. This super-enhancer, when activated, stimulates a range of genes leading to uncontrolled growth in pancreatic cancer. Importantly, the research team also found that a new experimental drug could inhibit this growth by counteracting the super-enhancer's effects.
Highlighting the significance of the discovery, Professor Ronald Evans, director of Salk’s Gene Expression Laboratory, said, “The discovery of this super-enhancer gives us both basic insight into PDAC and a new way to think of therapies.”
Enhancers are specific DNA regions that amplify the expression of genes. This amplification results in increased production of corresponding proteins. Super-enhancers, being highly active enhancers, can initiate a potent activation of numerous genes. This can lead to rapid cellular changes, such as accelerated growth.
In this study, the team led by Evans studied 16 human pancreatic cancer cell lines. They identified several super-enhancers, but one associated with the hnRNPF gene stood out due to its heightened activity in cancer cells compared to healthy cells. Subsequent experiments illustrated how the activation of hnRNPF initiated a series of cellular responses, amplifying the overall protein production in cells.
Corina Antal, who spearheaded the study, noted, “It’s well-established that cancer cells upregulate protein production in order to fuel their rapid growth. We have now identified how cells regulate this process at the super-enhancer level.”
Further experiments showed that removing the super-enhancer or the hnRNPF gene in cell lines could decelerate pancreatic cancer cell growth by a remarkable 80%. Additionally, an experimental drug aimed at Prmt1—a protein influenced by hnRNPF activation—proved effective in inhibiting pancreatic tumor growth both in lab settings and in mice.
Emphasizing the potential of this discovery, Michael Downes, a senior scientist at Salk, commented, “We were excited to find that there’s not a lot of redundancy in this super-enhancer pathway, which means there might be multiple ways to impact it with therapeutics. If you disrupt this network at any point, you have the same effect on blocking cellular growth.”
Another pivotal finding was the role of the Myc gene, which is associated with numerous cancers, including pancreatic. This gene can stimulate the hnRNPF super-enhancer. Historically, effective drugs counteracting Myc have been hard to come by. However, these findings hint at an alternative approach: targeting the super-enhancer-induced pathway.
Moreover, the team found that the hnRNPF super-enhancer was active in cells from a pancreatic cancer patient. Professor Evans added, “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.”
The research opens the door for further investigations to determine if drugs targeting this super-enhancer could be a viable treatment for pancreatic cancer patients.
Recently published in Nature Communications, Salk scientists elucidated the role of a certain "super-enhancer" in pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer. This super-enhancer, when activated, stimulates a range of genes leading to uncontrolled growth in pancreatic cancer. Importantly, the research team also found that a new experimental drug could inhibit this growth by counteracting the super-enhancer's effects.
Highlighting the significance of the discovery, Professor Ronald Evans, director of Salk’s Gene Expression Laboratory, said, “The discovery of this super-enhancer gives us both basic insight into PDAC and a new way to think of therapies.”
Enhancers are specific DNA regions that amplify the expression of genes. This amplification results in increased production of corresponding proteins. Super-enhancers, being highly active enhancers, can initiate a potent activation of numerous genes. This can lead to rapid cellular changes, such as accelerated growth.
In this study, the team led by Evans studied 16 human pancreatic cancer cell lines. They identified several super-enhancers, but one associated with the hnRNPF gene stood out due to its heightened activity in cancer cells compared to healthy cells. Subsequent experiments illustrated how the activation of hnRNPF initiated a series of cellular responses, amplifying the overall protein production in cells.
Corina Antal, who spearheaded the study, noted, “It’s well-established that cancer cells upregulate protein production in order to fuel their rapid growth. We have now identified how cells regulate this process at the super-enhancer level.”
Further experiments showed that removing the super-enhancer or the hnRNPF gene in cell lines could decelerate pancreatic cancer cell growth by a remarkable 80%. Additionally, an experimental drug aimed at Prmt1—a protein influenced by hnRNPF activation—proved effective in inhibiting pancreatic tumor growth both in lab settings and in mice.
Emphasizing the potential of this discovery, Michael Downes, a senior scientist at Salk, commented, “We were excited to find that there’s not a lot of redundancy in this super-enhancer pathway, which means there might be multiple ways to impact it with therapeutics. If you disrupt this network at any point, you have the same effect on blocking cellular growth.”
Another pivotal finding was the role of the Myc gene, which is associated with numerous cancers, including pancreatic. This gene can stimulate the hnRNPF super-enhancer. Historically, effective drugs counteracting Myc have been hard to come by. However, these findings hint at an alternative approach: targeting the super-enhancer-induced pathway.
Moreover, the team found that the hnRNPF super-enhancer was active in cells from a pancreatic cancer patient. Professor Evans added, “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.”
The research opens the door for further investigations to determine if drugs targeting this super-enhancer could be a viable treatment for pancreatic cancer patients.