Isoform switching as a key mechanism in chemotherapy resistance in triple-negative breast cancer
Uncover the secret to chemo resistance in triple-negative breast cancer: isoform switching disrupts DNA repair, empowering tumors to evade treatment. This discovery paves the way for personalized therapies targeting splicing patterns.
This study conducted a comprehensive transcriptome analysis of triple-negative breast cancer (TNBC) biopsies to investigate the role of alternative splicing in chemotherapy response. The researchers found that non-responders exhibited significantly higher rates of isoform switching, particularly in genes involved in DNA repair and immune pathways. A key finding was the shift towards a truncated XRCC3 isoform in non-responders, which likely impairs homologous recombination repair and contributes to chemotherapy resistance. These insights suggest that splicing alterations could serve as predictive biomarkers and guide the development of personalized therapies targeting the splicing machinery. Limitations include the small sample size and the need for further functional validation of the identified isoform switches.