The Role of BRCA1 in the Cellular Response to Chemotherapy

Germline mutations of the BRCA1 gene account for approximately 5% of breast and ovarian cancer cases, and lower than normal BRCA1 expression or function may be an important contributing factor in sporadic cancers. The major role of BRCA1 is to respond to DNA damage by participating in cellular pathw...

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Bibliographic Details
Published in:JNCI : Journal of the National Cancer Institute 2004-11, Vol.96 (22), p.1659-1668
Main Authors: Kennedy, Richard D., Quinn, Jennifer E., Mullan, Paul B., Johnston, Patrick G., Harkin, D. Paul
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biological and medical sciences
Biomarkers, Tumor - genetics
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Cancer
Cell Cycle Proteins - genetics
Chemotherapy
DNA damage
DNA Damage - drug effects
DNA Repair - drug effects
Female
Gene Expression Regulation, Neoplastic - drug effects
Genes
Genes, BRCA1 - drug effects
Genetic Markers
Germ-Line Mutation - drug effects
Humans
Medical sciences
Mutagens - toxicity
Mutation
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - genetics
Pharmacology. Drug treatments
Predictive Value of Tests
Research Design
Retrospective Studies
RNA, Messenger - drug effects
RNA, Neoplasm - drug effects
Spindle Apparatus - drug effects
Transcription, Genetic - drug effects
Tumors
Ubiquitins - metabolism
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Summary:Germline mutations of the BRCA1 gene account for approximately 5% of breast and ovarian cancer cases, and lower than normal BRCA1 expression or function may be an important contributing factor in sporadic cancers. The major role of BRCA1 is to respond to DNA damage by participating in cellular pathways for DNA repair, mRNA transcription, cell cycle regulation, and protein ubiquitination. Because most chemotherapeutic agents function by directly or indirectly damaging DNA, the role of BRCA1 as a regulator of chemotherapy-induced DNA damage has been the subject of an increasing number of investigations. We review published preclinical and clinical evidence that the level of BRCA1 function in an individual patient's tumor can guide the choice of chemotherapeutic agents for breast and ovarian cancer. We conclude that a loss of BRCA1 function is associated with sensitivity to DNA-damaging chemotherapy and may also be associated with resistance to spindle poisons. We recommend that prospective clinical studies investigating the role of BRCA1 in the response to chemotherapy be conducted.
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/djh312