Work

Roles of base and nucleotide excision repair activities in cancer treatment: implications for prognosis and resistance to therapy in breast and colorectal cancers

Year: 2026

Type: article

Abstract: 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. • BER and NER activities were reduced in untreated breast and colorectal cancer patients • BER and NER capacities increased post-treatment, in both cancer types • Higher DNA repair activity was associated with disease recurrence and metastasis • BER and NER responses differed by treatment type but often acted cooperatively • DNA repair profiling may improve prediction of resistance and guidance of personalized cancer therapy

Source: Mutation Research/Genetic Toxicology and Environmental Mutagenesis

DOI: 10.1016/j.mrgentox.2026.503923

Authors: Ana Rita Guedes, Carlos Martins-Gomes, Renato Cunha, Amélia M. Silva, Isabel Gaivão

Institutions: University of Trás-os-Montes and Alto Douro, Centro de Ciência Animal e Veterinária, Centro de Investigação e de Tecnologias Agro-Ambientais e Biologicas, Unidade Local de Saúde de Trás-os-Montes e Alto Douro

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,350