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Therapeutic Potential of Translational Readthrough at Disease-Associated Premature Termination Codons From Tumor

Leire Torices1, Caroline E Nunes-Xavier1,2,3, Rafael Pulido1,2,4

  • 1Biobizkaia Health Research Institute, Barakaldo, Spain.

IUBMB Life
|May 3, 2025
PubMed

Insights

Premature termination codons (PTCs) in tumor suppressor genes cause truncated proteins and mRNA decay. Pharmacological readthrough can restore full-length proteins, offering a potential cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tumor suppressor genes frequently acquire premature termination codons (PTCs) in cancers and hereditary cancer syndromes.
  • PTC mutations lead to truncated, unstable proteins and trigger mRNA degradation via nonsense-mediated decay.

Purpose of the Study:

  • To review recent advances in small molecule-induced translational readthrough for PTCs in tumor suppressor genes.
  • To discuss the therapeutic potential of this approach for hereditary syndromic cancers.

Main Methods:

  • Review of literature on small molecule drugs that induce translational readthrough.
  • Analysis of the impact of readthrough on protein restoration and mRNA stability.
  • Discussion of clinical relevance for specific cancer predisposition syndromes.

Main Results:

  • Pharmacological induction of translational readthrough can restore biosynthesis of full-length tumor suppressor proteins.
  • This approach stabilizes PTC-targeted mRNA, counteracting nonsense-mediated decay.
  • Small molecules show promise for treating cancers with specific PTC mutations.

Conclusions:

  • Pharmacological translational readthrough is a promising therapeutic strategy for cancers with PTCs in tumor suppressor genes.
  • This approach holds significant potential for patients with hereditary cancer syndromes.
  • Further research can advance this strategy for clinical application.

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