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JNCI Journal of the National Cancer Institute 2004 96(22):1659-1668; doi:10.1093/jnci/djh312
© 2004 by Oxford University Press
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© 2004 Oxford University Press

REVIEW

The Role of BRCA1 in the Cellular Response to Chemotherapy

Richard D. Kennedy, Jennifer E. Quinn, Paul B. Mullan, Patrick G. Johnston, D. Paul Harkin

Affiliation of authors: Department of Oncology, Cancer Research Centre, Queen's University Belfast, Belfast, Northern Ireland

Correspondence to: D. Paul Harkin, BSc, PhD, Department of Oncology, Cancer Research Centre, The Queen's University of Belfast, University Floor, Belfast City Hospital, Lisburn Rd., Belfast BT9 7AB, Northern Ireland (e-mail: d.harkin{at}qub.ac.uk)

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.


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Press Release: Researchers Call for Studies on Role of BRCA1 Mutations in Chemotherapy Response
Sarah L. Zielinski
J Natl Cancer Inst 2004 96: 1643. [Extract] [Full Text]



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