The DNA damage response (DDR) is crucial for maintaining genomic stability and preventing cancer development. Base excision repair (BER) and nucleotide excision repair (NER) play key roles in correcting oxidative and bulky DNA lesions, respectively. Alterations in these mechanisms have been implicated in breast and colorectal cancers (CRC), affecting both tumorigenesis and therapeutic responses. We have evaluated BER and NER activities in 85 cancer patients (58 breast cancer, 27 CRC) and 31 healthy controls. We used a comet assay-based approach to assess DNA repair capacity in peripheral blood lymphocytes. At diagnosis, patients exhibited lower BER and NER activities compared to controls, which suggests that impaired DNA repair mechanisms may contribute to cancer development. Following treatment, an overall increase in repair activity was observed, indicating cellular adaptation to therapy-induced DNA damage. This increase was greater in patients who later experienced relapse or metastasis, which suggests a possible link between enhanced repair capacity and treatment resistance. Our results also showed an interplay between BER and NER mechanisms, with their simultaneous activation potentially contributing to treatment resistance by enhancing tumour cell survival. These findings highlight the dual role of BER and NER in cancer progression and therapy outcomes, reinforcing their potential as biomarkers for predicting treatment response. Understanding the regulatory dynamics of these pathways may provide a foundation for improved personalized cancer treatment strategies.
Guedes et al. (Sun,) studied this question.