BRCA1--a good predictive marker of drug sensitivity in breast cancer treatment?
There are currently only two predictive markers of response to chemotherapy for breast cancer in routine clinical use, namely the Estrogen receptor-alpha and the HER2 receptor. The breast and ovarian cancer susceptibility gene BRCA1 is an important genetic factor in hereditary breast and ovarian cancer and there is increasing evidence of an important role for BRCA1 in the sporadic forms of both cancer types. Our group and numerous others have shown in both preclinical and clinical studies that BRCA1 is an important determinant of chemotherapy responses in breast cancer. In this review we will outline the current understanding of the role of BRCA1 as a determinant of response to DNA damaging and microtubule damaging chemotherapy. We will then discuss how the known functions of this multifaceted protein may provide mechanistic explanations for its role in chemotherapy responses.
Mullan
Paul B
PB
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Belfast, Northern Ireland, BT9 7AB, United Kingdom. p.mullan@qub.ac.uk
Gorski
Julia J
JJ
Harkin
D Paul
DP
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008870:Microtubules / Q000187:drug effects
D019313:BRCA1 Protein; D014408:Biomarkers, Tumor