THE ESSENTIAL
- Researchers have developed a method to target and degrade the Pin1 protein, involved in pancreatic cancer, whose five-year survival rate is only 11%.
- Dubbed “molecular crowbars,” these agents destabilize Pin1, making it vulnerable to cellular degradation. This approach aims not only to inhibit Pin1, but also to eliminate it entirely from cancer cells and tumor-associated fibroblasts.
- This approach also makes it possible to weaken tumor-associated fibroblasts, which protect cancer cells, and thus improve the effectiveness of treatments.
A team of researchers from the University of California at Riverside (United States) has developed an innovative method to target and degrade a protein called Pin1, a key player in the development of pancreatic cancer. Their study, published in the journal Proceedings of the National Academy of Sciences, could pave the way for more effective targeted therapies against this particularly aggressive disease, whose five-year survival rate is only 11%.
A key protein in the onset of pancreatic cancer
Pin1 is an enzyme involved in many cellular processes, and overactivated in several types of cancer, including pancreatic cancer. Its high presence in tumor-associated cancer cells and fibroblasts (the main cells of connective tissue) promotes tumor growth and progression. “Targeting Pin1 could help disrupt the tumor environment and make cancer cells more vulnerable to treatment”explain the researchers in a press release.
To tackle Pin1, the team designed molecular degraders, dubbed “molecular crowbars”. These agents bind tightly to the Pin1 protein and open its structure, making it unstable and “marked” for cellular degradation. According to the scientists, this approach represents unique therapeutic potential, as it aims not only to inhibit Pin1, but also to eliminate it entirely from cancer cells and tumor-associated fibroblasts.
Researchers were also interested in the interaction between pancreatic cancer cells and cancer-associated fibroblasts. These fibroblasts, support cells for tumor tissue, form a barrier that complicates treatment access to cancer cells. By reducing the activity of fibroblasts through the degradation of Pin1, researchers hope to make tumors more accessible to anticancer therapies.
A new therapeutic approach for difficult-to-treat cancers
The team of researchers is currently testing these “molecular crowbars” to measure their effectiveness in patients with pancreatic cancers or peritoneal metastases. The goal is to develop these molecular degraders into new treatments against difficult-to-treat cancers, using this new protein targeting modality. According to the authors of the study, this strategy could also be applied to other cancers where tumor-associated fibroblasts play a central role, thus opening new perspectives in the development of anticancer treatments.
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