Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer

Zagouri, Flora; Bournakis, Evangelos; Koutsoukos, Konstantinos; Papadimitriou, Christos

doi:10.3390/ph5091008

Cited by 55 publications

(32 citation statements)

References 78 publications

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“…Therefore, these pathways have a key role in resistance to aromatase inhibitors and also act as HSP90 client proteins. 71 Wong et al 72 suggested that HSP90 inhibitors are effective against aromatase inhibitor-resistant breast cancers. HSP90 is associated with various miRNAs, and miRNA-based inhibition of HSP90 is easier to achieve than miRNA-based HSP70 inhibition.…”

Section: Mirna In Hormone Receptor-positive/her2-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

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Section: Mirna In Hormone Receptor-positive/her2-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

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“…Consequently, many of the Hsp90 inhibitors previously mentioned have been examined at the clinical level as a novel chemotherapeutic intervention for HER2 positive breast carcinoma, with variable results being attained [78,44,79,80]. In the initial study of PU-H71, the agent demonstrated a very high propensity to initiate the degradation of HER2, and subsequently was notably cytotoxic against malignant, but not normal cells [21].…”

Section: Breast Carcinomamentioning

confidence: 99%

PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction

Trendowski

2015

Pharmacological Research

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Despite recent advances in precision medicine, many molecular-based antineoplastic agents do not potentiate sustainable long term remissions, warranting the investigation of novel therapeutic strategies. Heat shock protein 90 (Hsp90) is a molecular chaperone that not only has oncogenic properties, but also has distinct expression profiles in malignant and normal cells, providing a rational strategy to attain preferential damage. Prior attempts to target Hsp90 with natural product-based compounds have been hampered by their associated off target toxicities, suggesting that novel, fully synthetic inhibitors may be required to achieve the specificity necessary for therapeutic efficacy. Therefore, this review highlights the antineoplastic potential of PU-H71 (8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine), a novel purine based analog that has shown efficacy in many preclinical models of malignancy, and is now under clinical examination. In addition, the review suggests potential concomitant therapeutic approaches that may be particularly beneficial to molecular-based, as well as traditional cytotoxic cancer chemotherapy.

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“…HSP90 is frequently overexpressed and activated in cancer cells, including acute leukemias [41], gastrointestinal cancers [42], glioblastoma [43], cervical cancer [44], lung cancers [45] and human breast cancers [46]. Several studies have shown that HSP90 is localized in the cytoplasm and on the cell surface in certain types of cancer cells [47], including prostate cancer [48], melanomas [49], non-small-cell lung cancer cells [50], fibrosarcoma cells [51], lymphomas [52] and breast cancer cell [53].…”

Section: Discussionmentioning

confidence: 99%

Screening of Multiple Myeloma by Polyclonal Rabbit Anti-Human Plasmacytoma Cell Immunoglobulin

Zhang

Cai

et al. 2013

PLoS ONE

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Antibody-based immunotherapy has been effectively used for tumor treatment. However, to date, only a few tumor-associated antigens (TAAs) or therapeutic targets have been identified. Identification of more immunogenic antigens is essential for improvements in multiple myeloma (MM) diagnosis and therapy. In this study, we synthesized a polyclonal antibody (PAb) by immunizing rabbits with whole human plasmacytoma ARH-77 cells and identified MM-associated antigens, including enlonase, adipophilin, and HSP90s, among others, via proteomic technologies. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that 200 µg/mL PAb inhibits the proliferation of ARH-77 cells by over 50% within 48 h. Flow cytometric assay indicated that PAb treatment significantly increases the number of apoptotic cells compared with other treatments (52.1% vs. NS, 7.3% or control rabbit IgG, 9.9%). In vivo, PAb delayed tumor growth and prolonged the lifespan of mice. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that PAb also induces statistically significant changes in apoptosis compared with other treatments (P<0.05). We therefore conclude that PAb could be used for the effective screening and identification of TAA. PAb may have certain anti-tumor functions in vitro and in vivo. As such, its combination with proteomic technologies could be a promising approach for sieving TAA for the diagnosis and therapy of MM.

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Heat Shock Protein 90 (Hsp90) Expression and Breast Cancer

Cited by 55 publications

References 78 publications

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

PU-H71: An improvement on nature's solutions to oncogenic Hsp90 addiction

Screening of Multiple Myeloma by Polyclonal Rabbit Anti-Human Plasmacytoma Cell Immunoglobulin

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