Epitranscriptomic regulation in the progression of cancer and platinum resistance.

Abstract

Epitranscriptomic regulation has emerged as a critical mechanism in cancer biology, particularly in the development of chemoresistance. RNA modifications including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), 7-methylguanosine (m7G), pseudouridine (Ψ), and A-to-I editing dynamically control mRNA stability, splicing, translation, and degradation. RNA-modifying proteins called 'writers,' 'erasers,' and 'readers' regulate post-transcriptional networks to enable tumor adaptation and chemoresistance. In platinum-resistant tumors, epitranscriptomic changes modulate DNA damage response, apoptosis, drug efflux, and detoxification pathways. Preclinical studies demonstrate that pharmacological inhibition of key regulators, such as METTL3 inhibitors (STC-15, STM2457, UZH2) or FTO inhibitors, can sensitize tumors to platinum drugs and stimulate anti-tumor immunity. However, clinical translation remains limited by off-target effects, toxicity, and highly context-specific responses. Epitranscriptomic profiling may help identify novel biomarkers and guiding precision strategies to overcome chemoresistance.