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

Iwao-Koizumi, Kyoko; Matoba, Ryo; Ueno, Noriko; Kim, Seung Jin; Ando, Akiko; Miyoshi, Yasuo; Maeda, Eisaku; Noguchi, Shinzaburo; Kato, Kikuya

doi:10.1200/jco.2005.09.078

Cited by 254 publications

(160 citation statements)

References 28 publications

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“…This results in arresting the cell in the G 2 -M phase, which ultimately results in apoptosis. Nearly half of the treated patients with breast and ovarian cancer, however, do not respond to this microtubule-disrupting chemotherapy (2). Identification of cellular factors that are associated with the sensitivity to AMD treatment would have great clinical implications.…”

Section: Introductionmentioning

confidence: 99%

Synuclein γ Compromises Spindle Assembly Checkpoint and Renders Resistance to Antimicrotubule Drugs

Miao

Zhang

et al. 2014

Molecular Cancer Therapeutics

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Defects in the spindle assembly checkpoint (SAC) have been proposed to contribute to the chromosomal instability in human cancers. One of the major mechanisms underlying antimicrotubule drug (AMD) resistance involves acquired inactivation of SAC. Synuclein g (SNCG), previously identified as a breast cancer-specific gene, is highly expressed in malignant cancer cells but not in normal epithelium. Here, we show that SNCG is sufficient to induce resistance to AMD-caused apoptosis in breast cancer cells and cancer xenografts. SNCG binds to spindle checkpoint kinase BubR1 and inhibits its kinase activity. Specifically, the C-terminal (Gln106-Asp127) of SNCG binds to the N-terminal TPR (tetratricopeptidelike folds) motif of BubR1. SNCG-BubR1 interaction induces a structure change of BubR1, attenuates its interaction with other key checkpoint proteins of Cdc20, and thus compromises SAC function. SNCG expression in breast cancers from patients with a neoadjuvant clinical trial showed that SNCG-positive tumors are resistant to chemotherapy-induced apoptosis. These data show that SNCG renders AMD resistance by inhibiting BubR1 activity and attenuating SAC function. Mol Cancer Ther; 13(3); 699-713. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 99%

Synuclein γ Compromises Spindle Assembly Checkpoint and Renders Resistance to Antimicrotubule Drugs

Miao

Zhang

et al. 2014

Molecular Cancer Therapeutics

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“…Comprehensive gene expression profiles have enable to predict long-term outcome of individual breast cancer patients 2,3 and to define prognostic signatures to classify patients. 4,5 Predictive markers responsible for clinical outcome in treated patients 6,7 and pattern of resistances [8][9][10] have been further explored by gene expression profiling.…”

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confidence: 99%

A gene expression signature associated with metastatic cells in effusions of breast carcinoma patients

Dupont¹,

Gentien²,

Oberkampf³

et al. 2007

Intl Journal of Cancer

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Malignant effusion in invasive breast carcinoma is associated with poor prognosis. To decipher molecular events leading to metastasis and to identify reliable markers for targeted therapies are of crucial need. Therefore, we have used cDNA microarrays to delineate molecular signatures associated with metastasis and relapse in breast carcinoma effusions. Taking advantage of an immunomagnetic method, we have purified to homogeneity EpCAM-positive cells from 34 malignant effusions. Immunopurified cells represented as much as 10% of the whole cell fraction and their epithelial and carcinoma features were confirmed by immunofluorescence labeling. Gene expression profiles of 19 immunopurified effusion samples, were analyzed using human pan-genomic microarrays, and compared with those of 4 corresponding primary tumors, 8 breast carcinoma effusion-derived cell lines, and 4 healthy mammary tissues. Principal component and multiple clustering analyses of microarray data, clearly identified distinctive molecular portraits corresponding to the 4 categories of specimens. Of uppermost interest, effusion samples were arranged in 2 subsets on the basis of their gene expression patterns. The first subset partly shares a gene expression signature with the different cell lines, and overexpresses CD24, CD44 and epithelial cytokeratins 8,18,19. The second subset overexpresses markers related to aggressive invasive carcinoma (uPA receptor, S100A4, vimentin, CXCR4). These findings demonstrate the importance of using pure cell fractions to accurately decipher in silico gene expression of clinical specimens. Further studies will lead to the identification of genes of oustanding importance to diagnose malignant effusion, predict survival and tailor appropriate therapies to the metastatic effusion disease in breast carcinoma patients. ' 2007 Wiley-Liss, Inc.

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“…The use of expression arrays to derive molecular profiles that are predictive of clinical outcome has received great attention in the last 5 years (van't Veer et al, 2005;Reis-Filho et al, 2006b), especially in the neoadjuvant setting (Davidson and Morrow, 2005). Predictive signatures for different neoadjuvant chemotherapy regimens have been reported by some investigators but with less success by others (Chang et al, 2003;Ayers et al, 2004;Cleator and Ashworth, 2004;Chang et al, 2005a;Hannemann et al, 2005;Iwao-Koizumi et al, 2005;Modlich et al, 2005;Rouzier et al, 2005;Dressman et al, 2006;Reis-Filho et al, 2006b). Although some of these results are promising, issues related to the instability of mRNA, experimental design and data analysis have led many to call into question the validity of current approaches (Ransohoff, 2004;Brenton et al, 2005;Ioannidis, 2005;Reis-Filho et al, 2006b).…”

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confidence: 99%

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

et al. 2006

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We analysed the molecular genetic profiles of breast cancer samples before and after neoadjuvant chemotherapy with combination doxorubicin and cyclophosphamide (AC). DNA was obtained from microdissected frozen breast core biopsies from 44 patients before chemotherapy. Additional samples were obtained before the second course of chemotherapy (D21) and after the completion of the treatment (surgical specimens) in 17 and 21 patients, respectively. Microarray-based comparative genome hybridisation was performed using a platform containing B5800 bacterial artificial chromosome clones (genome-wide resolution: 0.9 Mb). Analysis of the 44 pretreatment biopsies revealed that losses of 4p, 4q, 5q, 12q13.11 -12q13.12, 17p11.2 and 17q11.2; and gains of 1p, 2p, 7q, 9p, 11q, 19p and 19q were significantly associated with oestrogen receptor negativity. 16q21 -q22.1 losses were associated with lobular and 8q24 gains with ductal types. Losses of 5q33.3 -q4 and 18p11.31 and gains of 6p25.1 -p25.2 and Xp11.4 were associated with HER2 amplification. No correlations between DNA copy number changes and clinical response to AC were found. Microarray-based comparative genome hybridisation analysis of matched pretreatment and D21 biopsies failed to identify statistically significant differences, whereas a comparison between matched pretreatment and surgical samples revealed a statistically significant acquired copy number gain on 11p15.2 -11p15.5. The modest chemotherapy-driven genomic changes, despite profound loss of cell numbers, suggest that there is little therapeutic selection of resistant non-modal cell lineages.

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

Abstract: 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.

Cited by 254 publications

References 28 publications

Synuclein γ Compromises Spindle Assembly Checkpoint and Renders Resistance to Antimicrotubule Drugs

Synuclein γ Compromises Spindle Assembly Checkpoint and Renders Resistance to Antimicrotubule Drugs

A gene expression signature associated with metastatic cells in effusions of breast carcinoma patients

Microarray-based comparative genomic hybridisation of breast cancer patients receiving neoadjuvant chemotherapy

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