WCSS Team Reveals Epigenetic Mechanism of Targeting DNMT1 to Achieve Enhanced Anticancer Efficacy and Reduced Toxicity in Treating Oral Squamous Cell Carcinoma
The research team led by Professor Hongmei Zhou and Assistant Researcher Jingjing Luo, from West China School of Stomatology (WCSS), Sichuan University, has made novel progress in revealing the epigenetic mechanism of DNMT1-mediated oral squamous cell carcinoma (OSCC) treatment. Their study was published in the top oncology journal, Molecular Cancer.
Molecularly targeted therapies are on the rise in treating OSCC. However, in clinical, single-targeted drugs often encounter resistance while multi-targeted drug combinations are associated with signal crosstalk, superimposed toxicity, side effects, etc. Therefore, it is crucial to investigate the growth-regulating mechanisms of OSCC and identify key targets to improve efficacy and reduce toxicity.
Professor Zhou’s team previously identified DNA methyltransferase 1 (DNMT1) as a potential key target in OSCC (Cancer Res, 2014). Disrupting the expression or activity of DNMT1 may lead to genome-wide DNA methylation disturbances, triggering a cascade of downstream signaling abnormalities. However, the exact molecular mechanisms in OSCC remain unresolved.
This research confirmed that DNMT1 and DNA methylation status are closely associated with oral carcinogenesis and OSCC progression. The team demonstrated that targeting DNMT1 triggers extensive DNA hypomethylation remodeling, enhancing tumor suppression effects and reducing hyperglycemia and insulin feedback toxicity in OSCC treatment.
In conclusion, their findings suggest that targeting the DNMT1-remodeled genome-wide DNA hypomethylation pattern can achieve enhanced anticancer efficacy and reduced toxicity by equilibrating signaling synergia. This study elucidates the epigenetic role of DNMT1 as a key multi-signal “gatekeeper” in controlling OSCC growth with minimal toxicity, confirming its potential as a therapeutic “lethal” target for OSCC.
WCSS is the only corresponding affiliation of this publication. Professor Hongmei Zhou and Assistant Researcher Jingjing Luo are co-corresponding authors. Dr. Yangfan Liu, Dr. Yu Sun, and Assistant Researcher Jin Yang are the co-first authors.
For more details, please click the link below.
https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-024-01993-1
