Current status of excision repair cross complementing-group 1 (ERCC1) in cancer.
Cisplatin, carboplatin and oxaliplatin are some of the most widely used anti-cancer agents in solid tumours. The cytotoxicity of platinating agents is directly related to their ability to cause DNA intra-strand crosslinks that trigger a series of intracellular events that ultimately result in cell death. DNA intra-strand crosslinks are processed and repaired by the nucleotide excision repair pathway. It is now clear that nucleotide excision repair (NER) capacity may have a major impact on the emergence of resistance, normal tissue tolerance and patient outcomes. ERCC1 is a key player in NER. In this review, we provide an overview of mammalian NER and then focus on biochemical, structural and pre-clinical aspects of ERCC1. We then present current clinical evidence implicating ERCC1 as a predictive and prognostic marker in cancer. Early evidence also suggests that ERCC1 or the pathways involved in the regulation of ERCC1 expression may be attractive anti-cancer targets. Such agents are expected to potentiate the cytotoxicity of platinating agents and could have a major impact on cancer therapy.
Gossage
Lucy
L
School of Molecular Medical Sciences, Academic Unit of Oncology, University of Nottingham, Nottingham University Hospitals, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK.
Madhusudan
Srinivasan
S
D014408:Biomarkers, Tumor / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D019008:Drug Resistance, Neoplasm; D004720:Endonucleases / Q000032:analysis*; D006801:Humans; D009369:Neoplasms / Q000737:chemistry* / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000627:therapeutic use*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; C071447:ERCC1 protein, human; D004720:Endonucleases