Telomir Pharmaceuticals demonstrates Telomir-1 reverses epigenetic gene silencing of STAT1, restoring tumor suppressor in human prostate cancer cells, outperforming chemotherapy and Rapamycin
- The co reported new preclinical results evaluating the effects of its lead candidate, Telomir-1, in a murine xenograft model using PC3 human prostate cancer cells. The data demonstrated that Telomir-1 reversed epigenetic silencing by DNA methylation of the STAT1 gene, a tumor suppressor and immune response regulator, in a dose-dependent manner. STAT1 is frequently silenced in advanced cancers via promoter hypermethylation, disrupting immune detection and apoptotic pathways.
- In this study, Telomir-1 administered orally daily for 21 days resulted in full reversal of STAT1 hypermethylation in tumor tissue. No such reversal was observed in the Paclitaxel (PTX) group, and only partial demethylation was observed with Rapamycin In addition to STAT1, Telomir-1 also reduced hypermethylation of TMS1 (also known as ASC or PYCARD), a pro-apoptotic tumor suppressor commonly silenced in prostate cancer. While PTX and Rapamycin showed comparable or greater effects on TMS1 methylation, Telomir-1 is unique in its ability to modulate both STAT1 and TMS1-two genes that together regulate immune response and apoptosis. Importantly, TMS1 also plays a central role in inflammasome activation, which not only contributes to tumor cell death but also supports the immune system's ability to detect and clear abnormal cells. When TMS1 is hypermethylated, this immune signaling pathway is disrupted-reducing caspase-1 activation and inflammatory cytokine release. This can impair immune surveillance and allow cancer cells to persist undetected. By reducing TMS1 hypermethylation, Telomir-1 may help restore immune recognition and enhance the tumor's sensitivity to both chemotherapy and immunotherapy.
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