# METTL3 inhibitor STM2457 plus enzalutamide curbs resistant prostate cancer growth in vivo

- Published: 2026-11-05 22:19 UTC
- Section: Life & Health › Medicine
- Tags: enzalutamide-resistant prostate cancer, ARv7 translation, m6A methylation, METTL3 inhibitor, STM2457, YTHDC2, lactate metabolism, androgen receptor
- URL: https://realtech.media/news/rt-be12d97307536f5c9b2594cf_mettl3_inhibitor_stm2457/

**Researchers described an m6A-dependent mechanism that raises ARv7 translation in enzalutamide-resistant prostate cancer; in vivo experiments tested blocking it.**

![METTL3 inhibitor STM2457 plus enzalutamide curbs resistant prostate cancer growth in vivo](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/fa8f966dd03765b8.jpg)
*Nikolay Kashpor, Wikimedia Commons, CC BY 4.0*

A study in Science Advances describes how enzalutamide-resistant prostate cancer sustains production of androgen receptor variant 7 (ARv7), a constitutively active transcription factor that drives disease progression. The authors identified ARv7 mRNA as a transcript carrying N6-methyladenosine (m6A) modifications. [1] Enzalutamide treatment increased METTL3-dependent m6A methylation of ARv7 mRNA at the A1177 site. [1]

The reader protein YTHDC2 recognizes this mark, which, according to the authors, enhances the translation efficiency of ARv7. [1] Resistant tumors also showed elevated lactate metabolism. It regulated AR transcription through promoter-mediated epigenetic modifications at H3K9 and H3K14. [1] Reactivated AR showed enhanced phase separation and up-regulated YTHDC2 expression at the transcriptional level, which closes the loop. [1]

In vivo experiments showed that targeting the METTL3-YTHDC2-ARv7 axis suppressed progression of enzalutamide-resistant disease. The METTL3 inhibitor STM2457 combined with enzalutamide inhibited tumor growth, and the authors observed no toxicity. [1] The results come from preclinical experiments.

The authors note that the ARv7 transcript is rare in castration-resistant prostate cancer, and this has limited recognition of its predictive value. They suggest that the clinical utility of ARv7 may need to be reconsidered in light of its m6A-dependent translational regulation. [1]

## Sources

1. [Science Advances](https://doi.org/10.1126/sciadv.aeg8317)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-be12d97307536f5c9b2594cf_mettl3_inhibitor_stm2457/