Kyoto University is seen in Kyoto’s Sakyo Ward. (Mainichi/Yuki Noguchi)
OSAKA — A mechanism by which pancreatic cancer, known as a difficult-to-treat form of cancer, becomes malignant has been uncovered by a Kyoto University research team.
According to research published June 2 in the online edition of the Journal of Clinical Investigation, certain genes regulate the expression of proteins that facilitate the spread of cancer.
Pancreatic cancer is hard to detect at an early stage and easily spreads to other organs such as the liver, with the five-year survival rate standing at just 8.5% — the lowest among all cancers. Highly differentiated pancreatic cancers, which closely resemble the structure and function of the original cells, tend to respond well to anticancer drugs. In contrast, poorly differentiated or undifferentiated pancreatic cancers, whose cells are very different from the original, are highly malignant, and no effective treatments have been established for them.
The research team began by analyzing diseased tissues from pancreatic cancer patients. They discovered that many poorly differentiated and undifferentiated cancers have low levels of a gene, Polybromo 1 (PBRM1), which regulates the expression of specific proteins. They then compared the development rates of poorly differentiated and undifferentiated cancers in mice genetically engineered to develop pancreatic cancer based on whether the PBRM1 gene was present. Only one out of 16 mice with PBRM1 developed these types of cancer, while all 20 mice lacking PBRM1 did so.
They also found that PBRM1 regulates the expression of vimentin, a protein that facilitates the spread, or metastasis, of cancer to other parts of the body. In mice lacking PBRM1, vimentin levels increased, resulting in the formation of poorly differentiated and undifferentiated cancers. This same relationship was observed in human pancreatic cancer cases.
The researchers next administered drugs to block vimentin expression in mice lacking PBRM1, and found that poorly differentiated cancers transformed into highly differentiated ones and metastasis decreased.
Based on these results, the team intends to begin clinical trials administering vimentin inhibitors to patients one year from now.
Kyoto University Hospital’s Akihisa Fukuda, a gastroenterology specialist and associate professor who was part of the research team, commented, “Hopefully, this will lead to effective treatments for highly malignant pancreatic cancer.”
(Japanese original by Sonoko Nakamura, Osaka Lifestyle, Science & Environment News Department)
AloJapan.com