New Insights into Targeting Pancreatic Cancer

The Role of Perlecan

A molecule produced by fibroblasts, known as perlecan, may provide a crucial target for the treatment of pancreatic cancer. This aggressive form of cancer has a dismal survival rate of only 7% at five years post-diagnosis and is among the leading causes of cancer-related deaths. Current treatment options yield an average survival of less than one year, primarily due to the lack of prominent signs and symptoms in the early stages of the disease. By the time pancreatic cancer is diagnosed, it often has metastasized to other body parts, highlighting the urgent need for new therapeutic strategies.

Recent Research Findings

A recent study published in *Nature Communications* by a collaborative team of scientists from Australia, the United States, and the United Kingdom sheds light on how pancreatic cancer tumors spread. Utilizing mouse models, the researchers focused on cancer-associated fibroblasts to understand their influence on cancer dissemination.

The study revealed that cancer cells with mutations in the p53 gene can ‘educate’ nearby fibroblasts to create an environment conducive to their spread. This interaction allows even a small number of aggressive cancer cells to enhance the spread of less aggressive ones. Additionally, these aggressive cells manipulate and remodel surrounding tissues, providing a shield against chemotherapy. One significant mechanism identified is the production of perlecan.

Impact of Reducing Perlecan Levels

In their experiments, the scientists reduced perlecan levels in pancreatic cancer mouse models. The results indicated a significant decrease in cancer spread and an improved response of the tumors to chemotherapy.

These findings underscore the potential of targeting perlecan and other similar molecules in the tumor microenvironment as a new therapeutic approach. Traditionally, cancer treatments have focused on the cancer cells themselves, with limited research on their surrounding environment. By exploring the role of perlecan, researchers may develop effective strategies not only for pancreatic cancer but also for other malignancies, such as prostate and breast cancer.

Conclusion

This research opens the door to novel therapeutic targets for pancreatic cancer treatment, emphasizing the importance of understanding the tumor microenvironment. Continued exploration in this area could lead to improved outcomes for patients facing this challenging disease.

References

Vennin, C., Mélénec, P., Rouet, R., Nobis, M., Cazet, A. S., Murphy, K. J., . . . Timpson, P. (2019). CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. *Nature Communications*, 10(1). doi:10.1038/s41467-019-10968-6

Key to targeting the spread of pancreatic cancer. (2019, August 12). Retrieved from https://www.eurekalert.org/pub_releases/2019-08/giom-ktt080719.php

Image credit: Max Nobis