Epitranscriptomic regulation in the progression of cancer and platinum resistance

Pavol Harvanik1, Terézia Hudáková1, Martina Šemeláková1

  • 1Department of Medical Biology, Faculty of Medicine, P. J. Šafárik University in Košice, Košice, Slovakia.

Insights

Epitranscriptomic modifications regulate cancer chemoresistance. Targeting RNA regulators like METTL3 or FTO shows promise in preclinical studies for sensitizing tumors to platinum drugs.

Area of Science:

  • Cancer Biology
  • Molecular Biology
  • Genetics

Background:

  • Epitranscriptomic regulation, involving dynamic RNA modifications (e.g., m6A, m5C, m1A, m7G, Ψ, A-to-I editing), is crucial in cancer.
  • RNA-modifying proteins ('writers,' 'erasers,' 'readers') control post-transcriptional networks, influencing tumor adaptation and chemoresistance.

Purpose of the Study:

  • To explore the role of epitranscriptomic changes in platinum-resistant tumors.
  • To investigate the potential of targeting epitranscriptomic regulators for overcoming chemoresistance.

Main Methods:

  • Review of preclinical studies on epitranscriptomic regulation in cancer.
  • Analysis of RNA modification roles in platinum-resistant tumor pathways (DNA damage response, apoptosis, drug efflux, detoxification).

Main Results:

  • Epitranscriptomic alterations are implicated in platinum resistance by modulating key cellular pathways.
  • Pharmacological inhibition of METTL3 or FTO demonstrates preclinical efficacy in sensitizing tumors to platinum drugs and enhancing anti-tumor immunity.

Conclusions:

  • Epitranscriptomic profiling offers potential for identifying biomarkers and guiding precision medicine strategies against chemoresistance.
  • Clinical translation of epitranscriptomic therapies is hindered by off-target effects, toxicity, and context-specific responses.

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