Professor Masaaki Komatsu and Specially Appointed Assistant Professor Tetsuya Saito of the Graduate School of Medical and Dental Sciences, Niigata University have elucidated the mechanism by which hepatocellular carcinoma grows and make hepatocellular carcinoma malignant with a new compound that cancels the mechanism. Announced that it succeeded in suppressing.This result was obtained through joint research with the University of Tokyo and Keio University.
Hepatocellular carcinoma is a malignant tumor that originates in liver tissue and is the third leading cause of cancer death in Japan.It is said to be caused by long-term drinking and persistent infection with hepatitis B and C viruses.In addition, since there are few symptoms, there are many cases in which the disease is progressing when it is discovered, and the recurrence rate is high.Even now, it is said that sufficient treatment is difficult.
It is known that cancer cells of patients with hepatocellular carcinoma contain a large amount of structures called Mallory bodies, but their functions are unknown.Here, we have found that the protein p62 / SQSTM1, which is the main component of this structure, has a mechanism to enhance the growth of hepatocellular carcinoma and resistance to anticancer drugs. p62 / SQSTM1 binds to a protein called KEAP2 that leads to degradation of the transcription factor protein NRF1, and constantly activates NRF2.It is said that this activation of NRF2 causes the growth of hepatocellular carcinoma and resistance to anticancer drugs.
Furthermore, it was confirmed that the novel compound counteracts the mechanism of NRF62 activation by p1 / SQSTM2, suppresses the growth of hepatocellular carcinoma cells, and enhances the efficacy of existing anticancer agents.This new compound is called K67 and was discovered in collaboration with the University of Tokyo Drug Discovery Organization.
The research team is currently developing a K67 derivative that enhances the efficacy of K67 for clinical application, and a drug targeting NRF2 itself.These drugs are expected as therapeutic agents for hepatocellular carcinoma.
