Nucleotide excision repair pathways involved in cisplatin resistance in non-small-cell lung cancer
| Autor: | Agustí Barnadas, Rafael Rosell, Carme Sarries, Miquel Taron, Barbara Roig, Giorgio V. Scagliotti |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Genetic Markers
Lung Neoplasms DNA Repair DNA repair Drug Resistance Gene Expression Antineoplastic Agents Drug resistance DNA-binding protein 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung Gene expression Carcinoma medicine Humans Lung cancer Non-Small-Cell Lung Clinical Trials as Topic Cisplatin Drug Resistance Neoplasm Proteins DNA-Binding Proteins Endonucleases Hematology Oncology business.industry General Medicine medicine.disease Molecular biology respiratory tract diseases Genetic marker 030220 oncology & carcinogenesis Cancer research Neoplasm 030211 gastroenterology & hepatology business Nucleotide excision repair |
| Popis: | In spite of the growing list of genetic abnormalities identified as being involved in DNA repair pathways that alter chemosensitivity in non-small-cell lung cancer (NSCLC) patients, translational assays have not yet been developed for use in individualized chemotherapy.In metastatic NSCLC, no single cisplatin-based chemotherapy regimen has been shown to be superior to any other. Although these studies show a small survival tail at 3 years, the majority of patients had a median survival of 8 to 10 months. We review the principal mechanisms of cisplatin resistance, particularly those involved in the nucleotide excision repair (NER) pathways (transcription-coupled repair and global genomic repair).ERCC1 is a single-stranded DNA endonuclease that forms a tight heterodimer with xeroderma pigmentosum complementation group F. It incises DNA on the 5' side of a lesion such as cisplatin-DNA adduct. Therefore, overexpression of ERCC1 and other NER enzymes during ovarian cancer chemotherapy with cisplatin appears to be implicated in the formation of cellular and clinical drug resistance. Recently, baseline ERCC1 mRNA overexpression has been related to poor response and survival in cisplatin-treated NSCLC patients.The level of evidence for many assays is limited, and only ERCC1 mRNA levels have been analyzed extensively. The impact of ERCC1 should be fully validated in prospective clinical trials. |
| Databáze: | OpenAIRE |
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