A team led by Ajou University Professor Sang Min Jeon (College of Pharmacy, pictured above) found that clobetasol propionate, an ointment substance used to treat skin problems, is very effective at containing NRF2 (Nuclear factor E2-Related Factor 2), a gene that causes lung cancer. The team’s findings were published on May 15th in the online edition of Oncogene, which is a sister journal of Nature and internationally recognized as an authority specializing in oncology (IF 7.93), under the title of "A Clinical Drug Library Screen Identifies Clobetasol Propionate as an NRF2 Inhibitor with Potential Therapeutic Efficacy in KEAP1 Mutant Lung Cancer."

There have been worldwide efforts to develop anti-cancer agents targeting NRF2, which also creates tolerance to existing anti-cancer drugs and radiation therapy. However, no anti-cancer agent that can control NRF2 has been discovered.

In the latest research, Professor Jeon's team adopted the drug repositioning strategy that uses the catalogue of about 4,000 compounds for clinical purposes to streamline the drug-development process. In the process, he confirmed that steroid series agents are generally effective in controlling NRF2 and clobetasol propionate is the most powerful among them.

Clobetasol propionate’s mechanism blocks the decomposition of NRF2 protein, which is dependent on GSK3-βTrCP, and its movement into the nucleus by combining with the glucocorticoid receptor, a kind of nuclear receptor.

Professor Jeon said, "Our findings are a first in that we identified the strongest agent in containing NRF2 from among those now being used in clinical tests, and the agent’s strong anti-cancer effect has been proved in animal testing," adding, "I expect that clinical tests for developing anti-cancer drugs using clobetasol propionate will be possible before long, since a wealth of clinical data on its side effects and reliability has been collected while being used as a skin ailment drug."

The research was conducted with the support of the Research and Development Project to Conquer Cancer carried out by the Ministry of Health and Welfare, and the Basic Research Support Project (for individuals) carried out by the Ministry of Science, ICT and Future Planning. Eun Ji Choi (co-first author, master's and doctoral combined course at Ajou University), Byeong Jin Jung (co-first author, master's course at Ajou University), Hwan Shik Yoo (coauthor, master's course at Ajou University), Eun Ae Shin (coauthor, master's course at Ajou University), and researchers from other universities participated in the research.