Observational analysis identified genetic markers for neoadjuvant chemoradiotherapy response in rectal cancer, suggesting potential biomarkers for treatment personalization.
Background Neoadjuvant chemoradiotherapy (nCRT) is essential for treating locally advanced rectal cancer (LARC), however response to nCRT varies, and reliable predictors are lacking. Methods This study used whole exome sequencing analysis to investigate genetic differences between tumors highly responsive and non‐responsive to nCRT. Five patients with good response and two patients without response to nCRT were used as a discovery set. Results The analysis identified 15 InDels and 202 non‐synonymous SNVs exclusively present in tumors of non‐responders, mainly in genes regulating the cell cycle, adhesion, and migration. In contrast, 9 InDels and 122 non‐synonymous SNVs were exclusively present in tumors of good responders, primarily in extracellular matrix remodeling and immunity‐related genes. Six variants in transmembrane transporter genes were selected as candidate biomarkers and validated in 33 LARC patients. Conclusion The results suggest that SLC16A6 rs7222013 and SLC25A2 rs3749780 may serve as potential predictors of poor nCRT response in LARC patients.
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Kostic et al. (2025) studied this question.
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