[Prediction of response to docetaxel in breast cancer].
Docetaxel, a second-generation taxane, is one of the most powerful anticancer drugs for breast cancer. It has been widely used in the metastatic setting but also in the adjuvant or neoadjuvant setting for breast cancer patients. However, docetaxel is not effective for all breast cancers. The response rate is 40-60% even in first-line chemotherapy and it decreases to 20-30% in the second-or third-line chemotherapy. Therefore, it is very important to predict the sensitivity of docetaxel with high accuracy in order to avoid unnecessary treatment. Docetaxel binds to beta-tubulin and promotes polymerization, resulting in interference with mitosis. Unfortunately, the mechanism of sensitivity or resistance to docetaxel has not been fully understood. Recent studies in this area have demonstrated various mechanisms involved in the anti-tumor activity of docetaxel: (1) efflux (p-glycoprotein), (2) metabolism (CYP3A4), (3) beta-tubulin (isotype class I and III), (4) cell cycle (HER2, BRCA1), (5) apoptosis (p53, Bcl-2, thioredoxin), and (6) cell proliferation (MIB-1, nuclear grade). In addition, recently, gene expression profiling has been applied to the prediction of response to docetaxel in breast cancer. This work has reviewed recent studies, including ours, which have evaluated the association between these biological parameters and response to docetaxel in breast cancer.
Kim
Seung Jin
SJ
Dept. of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University.
Noguchi
Shinzaburo
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011379:Prognosis; D043823:Taxoids / Q000627:therapeutic use*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D054316:Biomarkers, Pharmacological; D043823:Taxoids; D000077143:Docetaxel