Researchers at MUSC Hollings Cancer Center have made a significant breakthrough in the fight against pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer.
Published in the journal Cell Death and Differentiation, their study unveils a new strategy that could potentially curb the growth of pancreatic tumors.
Pancreatic cancer is notoriously aggressive and difficult to treat, with a grim five-year survival rate of just 13%.
This poor prognosis is projected to make PDAC the second-leading cause of cancer-related deaths by 2030. In light of these daunting statistics, the findings from the Barnoud Lab at Hollings offer a glimmer of hope.
Led by Tim Barnoud, Ph.D., who recently joined Hollings in 2021, the research team focused on the role of heat shock protein 70 (HSP70) in cancer cells.
Heat shock proteins, which act as molecular chaperones, ensure proper protein folding and function during cellular stress.
Cancer cells, which grow at an unusually rapid rate and often endure harsh conditions such as low oxygen and nutrient levels, produce more HSP70 than normal cells.
Barnoud’s previous work at The Wistar Institute revealed an unusual abundance of HSP70 in the mitochondria of tumor cells—contrary to its absence in the mitochondria of healthy cells.
Mitochondria are crucial as they generate most of the cell’s energy supply, and their dysfunction can influence cancer progression and metastasis.
In their groundbreaking study, Barnoud and his team discovered that inhibiting HSP70 impairs the function of a protein called DRP1, essential for maintaining mitochondrial health.
This impairment leads to an accumulation of defective mitochondria, which can trigger the death of cancer cells.
However, they found that HSP70 inhibition also causes an increase in reactive oxygen species and oxidative stress, activating a survival pathway in the cancer cells called autophagy.
Autophagy, often referred to as “self-eating,” is a process where cells break down their own components to survive stress conditions.
Fascinatingly, the team observed that when autophagy was blocked, the effects of HSP70 inhibition on pancreatic tumors were enhanced, slowing their growth significantly in mouse models.
This dual-target approach appears more effective, aligning with the principle that multi-faceted treatments tend to yield better results in cancer therapy.
The implications of these findings are substantial. There is already an FDA-approved drug that can block autophagy, and more potent, autophagy-specific inhibitors are currently being tested in clinical trials for pancreatic cancer.
The ultimate aim of Barnoud’s lab is to advance the development of a small molecule HSP70 inhibitor, which they hope will not only be a valuable tool against pancreatic cancer but may also have potential applications in other cancers that heavily rely on HSP70.
This research not only highlights a potentially vital therapeutic target in pancreatic cancer but also illustrates the complex interplay of cellular mechanisms that can be leveraged to develop more effective cancer treatments.
As the Barnoud Lab continues to explore these pathways, their work could lead to significant advancements in the management of one of the most challenging cancers to treat.
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The research findings can be found in Cell Death & Differentiation.
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