Hsp90 — a potential prognostic marker in CML

Žáčková, Markéta; Moučková, Darina; Lopotová, Tereza; Ondrackova, Zuzana; Klamová, Hana; Moravcová, Jana

doi:10.1016/j.bcmd.2012.11.002

Cited by 37 publications

(23 citation statements)

References 29 publications

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“…The family is composed of five members that are encoded by the HSPC1-5 genes [ 16 ]. Overexpression of HSP90 has been reported in multiple cancer types [ 8 , 97 , 98 ] and elevated expression is associated with poor prognosis in lung, esophageal, bladder cancers, melanoma, and leukemia [ 99 , 100 , 101 , 102 ]. HSP90 is significantly overexpressed in medulloblastoma, the most malignant pediatric brain cancer, which is also characterized by a marked positive correlation between HSP70 and HSP90 expression [ 103 ].…”

Section: Hsps and Their Role As Molecular Chaperones In Aiding Malmentioning

confidence: 99%

Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach

Chatterjee

Burns

2017

IJMS

422

288

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Heat shock proteins (HSPs) are a large family of chaperones that are involved in protein folding and maturation of a variety of “client” proteins protecting them from degradation, oxidative stress, hypoxia, and thermal stress. Hence, they are significant regulators of cellular proliferation, differentiation and strongly implicated in the molecular orchestration of cancer development and progression as many of their clients are well established oncoproteins in multiple tumor types. Interestingly, tumor cells are more HSP chaperonage-dependent than normal cells for proliferation and survival because the oncoproteins in cancer cells are often misfolded and require augmented chaperonage activity for correction. This led to the development of several inhibitors of HSP90 and other HSPs that have shown promise both preclinically and clinically in the treatment of cancer. In this article, we comprehensively review the roles of some of the important HSPs in cancer, and how targeting them could be efficacious, especially when traditional cancer therapies fail.

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Section: Hsps and Their Role As Molecular Chaperones In Aiding Malmentioning

confidence: 99%

Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach

Chatterjee

Burns

2017

IJMS

422

288

View full text Add to dashboard Cite

show abstract

“…HSP90 is overexpressed in various cancer types, including pancreatic, ovarian, breast, lung and endometrial cancer, as well as oropharyngeal SCC and multiple myeloma (4–7). High expression of HSP90 was indicated to be a marker of poor prognosis in lung cancer, esophageal cancer, bladder cancer, melanoma and leukemia (8–11). Combination therapy with HSP90 inhibitors and conventional photon radiation delays tumor growth more effectively than radiotherapy alone (12).…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of the mRNA expression of members of the HSP90 family in non‑small cell lung cancer

Liu

Kang

et al. 2019

Exp Ther Med

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The aim of the present study was to investigate the potential prognostic value of members of the heat shock protein (HSP)90 family in non-small cell lung cancer (NSCLC) patients. The mRNA expression profiles of 1,926 NSCLC patients, which was available from the Kaplan-Meier plotter database, were included in the study. High expression of HSP90AA1 mRNA was significantly associated with a poorer rate of overall survival (OS) for all NSCLC patients [hazard ratio (HR), 1.21; 95% confidence interval (CI): 1.06–1.37; P=0.004], as well as for patients with adenocarcinoma (ADE; HR, 1.3; 95% CI: 1.02–1.65; P=0.034), but no significant correlation was identified for squamous cell carcinoma (SCC) patients (HR, 1.08; 95% CI: 0.85–1.38; P=0.51). High expression of HSP90AB1 and HSP90B1 mRNA was significantly associated with poorer rates of OS in lung SCC and ADE patients combined, as well as in lung ADE patients alone. By contrast, high expression of tumor necrosis factor receptor-associated protein 1 (TRAP1) mRNA was significantly associated with improved OS rates in all NSCLC patients combined (HR, 0.88; 95% CI: 0.77–0.99; P=0.041), as well as ADE patients. In stratified survival analysis, a high expression of HSP90AA1, HSP90AB1 and HSP90B1 predicted poor prognosis in stage I NSLCC patients, suggesting that these genes may serve as stage-independent prognostic indicators. As an elevated expression of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 was associated with poorer OS outcomes in patients with NSCLC, these HSP90 members may be potential prognostic biomarkers and drug targets for the treatment of NSCLC.

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“…In addition, bioinformatic analyses have revealed that Hsp90 is enriched in patients harboring FLT3 internal tandem duplications (FLT3-ITD) [122]. Hsp90 has also been correlated with the disease state in CML and, thus, has been proposed to serve as a risk factor [123]. In vitro exposure of primary CD34 + AML cells and AML-derived cell lines to the Hsp90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has been found to inhibit growth, apoptosis and cell cycle arrest without affecting normal CD34 + cells [124].…”

Section: Targeting Leukemia Stem Cellsmentioning

confidence: 99%

Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer

et al. 2016

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Background Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized by high self-renewal and multi-lineage differentiation capacities. CSCs are thought to play indispensable roles in the initiation, progression and metastasis of many types of cancer. Leukemias are thought to be initiated and maintained by a specific sub-type of CSC, the leukemia stem cell (LSC). An important feature of LSCs is their resistance to standard therapy, which may lead to relapse. Increasing efforts are aimed at developing novel therapeutic strategies that selectively target LSCs, while sparing their normal counterparts and, thus, minimizing adverse treatment-associated side-effects. These LSC targeting therapies aim to eradicate LSCs through affecting mechanisms that control their survival, self-renewal, differentiation, proliferation and cell cycle progression. Some LSC targeting therapies have already been proven successful in pre-clinical studies and they are now being tested in clinical studies, mainly in combination with conventional treatment regimens. Conclusions A growing body of evidence indicates that the selective targeting of LSCs represents a promising approach to improve disease outcome. Beyond doubt, the CSC hypothesis has added a new dimension to the area of anticancer research, thereby paving the way for shaping a new trend in cancer therapy.

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Hsp90 — a potential prognostic marker in CML

Cited by 37 publications

References 29 publications

Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach

Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach

Prognostic value of the mRNA expression of members of the HSP90 family in non‑small cell lung cancer

Novel strategies for targeting leukemia stem cells: sounding the death knell for blood cancer

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