Researchers mainly from Kyoto University have found that the impaired function of a specific gene contributes to the malignancy of pancreatic cancer, which is hard to treat with chemotherapy.
They said the reduced gene function increases a protein that promotes metastasis and that existing drugs may be effective in suppressing the protein’s functions. The finding was published in the Journal of Clinical Investigation in June.
Pancreatic cancer is the third-leading cause of cancer death in Japan. The five-year survival rate for the cancer is 8.5%, the worst among any cancer.
Malignant cases account for 30% to 40%, but the underlying mechanisms had not been well understood.
The team examined pancreatic cancer tissue removed during surgery and found that the decline in function of Polybromo 1 — or PBRM1, a gene that regulates the expression of various proteins — is linked to greater malignancy and a higher risk of relapse.
A genetic modification to disable PBRM1 in mice with pancreatic cancer resulted in a higher malignancy rate, increased metastases and shorter survival.
The cancer cells showed an increased level of vimentin, a protein that promotes metastasis. Meanwhile, the malignancy rate and metastases decreased after mice were given a drug that suppresses vimentin.
Such correlations were also confirmed in human pancreatic cancer.
The research “has shown that drugs to suppress vimentin effects may lead to a new treatment for highly malignant pancreatic cancer,” Kyoto University associate professor Akihisa Fukuda said. “We hope to conduct clinical trials to realize early practical application.”