Prediction of Docetaxel Response in Human Breast Cancer by Gene Expression Profiling

• Kyoko Iwao-Koizumi

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Ryo Matoba

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Noriko Ueno

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Seung Jin Kim

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Akiko Ando

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Yasuo Miyoshi

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Eisaku Maeda

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Shinzaburo Noguchi

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

• Kikuya Kato

  From the Taisho Laboratory of Functional Genomics, Nara Institute of Science and Technology, Nara; Department of Surgical Oncology, Osaka University Medical School, Osaka; and NTT Communication Science Laboratories, Kyoto, Japan

抄録

Docetaxel is one of the most effective anticancer drugs available in the treatment of breast cancer. Nearly half of the treated patients, however, do not respond to chemotherapy and suffer from side effects. The ability to reliably predict a patient's response based on tumor gene expression will improve therapeutic decision making and save patients from unnecessary side effects. A total of 44 breast tumor tissues were sampled by biopsy before treatment with docetaxel, and the response to therapy was clinically evaluated by the degree of reduction in tumor size. Gene expression profiling of the biopsy samples was performed with 2,453 genes using a high-throughput reverse transcriptase polymerase chain reaction technique. Using genes differentially expressed between responders and nonresponders, a diagnostic system based on the weighted-voting algorithm was constructed. This system predicted the clinical response of 26 previously unanalyzed samples with over 80% accuracy, a level promising for clinical applications. Diagnostic profiles in nonresponders were characterized by elevated expression of genes controlling the cellular redox environment (ie, redox genes, such as thioredoxin, glutathione-S-transferase, and peroxiredoxin). Overexpression of these genes protected cultured mammary tumor cells from docetaxel-induced cell death, suggesting that enhancement of the redox system plays a major role in docetaxel resistance. These results suggest that the clinical response to docetaxel can be predicted by gene expression patterns in biopsy samples. The results also suggest that one of the molecular mechanisms of the resistance is activation of a group of redox genes.

収録刊行物

• Journal of Clinical Oncology

  Journal of Clinical Oncology 23 (3), 422-431, 2005-01-20

  American Society of Clinical Oncology (ASCO)

キーワード

• Cancer Research
• Oncology

詳細情報

• CRID: 1361699993566375296
• NII論文ID: 30022791445
• DOI: 10.1200/jco.2005.09.078
• ISSN: 15277755
• ISSN: 0732183X
• Web Site: https://ascopubs.org/doi/pdfdirect/10.1200/JCO.2005.09.078
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