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Updated: May 17, 2026
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Cancer syndromes and therapy by stop-codon readthrough
Renata Bordeira-Carriço1, Ana Paula Pêgo, Manuel Santos
1Institute of Molecular Pathology and Immunology of the University of Porto, Portugal.
Abstract:
Several hereditary cancer syndromes are associated with nonsense mutations that create premature termination codons (PTC). Therapeutic strategies involving readthrough induction partially restore expression of proteins with normal function from nonsense-mutated genes, and small molecules such as aminoglycosides and PTC124 have exhibited promising results for treating patients with cystic fibrosis and Duchenne muscular dystrophy. Transgenic expression of suppressor-tRNAs and depleting translation termination factors are, among others, potential strategies for treating PTC-associated diseases. In this review, the potential of using readthrough strategies as a therapy for cancer syndromes is discussed, and we consider the effect of nonsense-mediated decay and other factors on readthrough efficiency.
Insights
Readthrough strategies can restore protein function in hereditary cancer syndromes caused by premature termination codons (PTC). This review explores therapeutic potential and challenges like nonsense-mediated decay.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- Hereditary cancer syndromes often arise from nonsense mutations creating premature termination codons (PTCs).
- Restoring functional protein expression is a key therapeutic goal for these genetic disorders.
- Current research explores various strategies to overcome the effects of PTCs.
Purpose of the Study:
- To review the potential of readthrough strategies for treating cancer syndromes associated with PTCs.
- To discuss the efficacy and challenges of different readthrough induction methods.
- To analyze factors influencing readthrough efficiency, including nonsense-mediated decay.
Main Methods:
- Literature review of therapeutic strategies for PTC-associated diseases.
- Analysis of small molecules (e.g., aminoglycosides, PTC124) and genetic approaches (e.g., suppressor-tRNAs).
- Evaluation of factors affecting readthrough efficiency in cancer contexts.
Main Results:
- Readthrough induction strategies show promise in preclinical models for genetic diseases like cystic fibrosis and Duchenne muscular dystrophy.
- Various methods, including small molecules and genetic manipulations, can induce readthrough of PTCs.
- Nonsense-mediated decay (NMD) and other cellular mechanisms can significantly impact the efficiency of readthrough therapies.
Conclusions:
- Readthrough strategies represent a viable therapeutic avenue for hereditary cancer syndromes linked to PTCs.
- Optimizing readthrough efficiency and overcoming resistance mechanisms like NMD are critical for clinical success.
- Further research is needed to fully harness the potential of readthrough therapies for cancer treatment.
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