Kyoto ¨C 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 ¡ª or PBRM1, a gene that regulates the expression of various proteins ¡ª 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.¡±
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