Therapeutic potency of heat-shock protein-90 pharmacological inhibitors in the treatment of gastrointestinal cancer, current status and perspectives

Boroumand, Nadia; Saghi, Hossein; Avan, Amir; Bahreyni, Amirhossein; Ryzhikov, Mikhail; Hassanian, Seyed Mahdi

doi:10.1111/jphp.12824

Cited by 15 publications

(13 citation statements)

References 55 publications

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“…In pancreatic tumor models, the HSP90 inhibitors, NVP-AUY922 and ganetespib, were shown to suppress angiogenesis and tumor growth [161,162], whereas geldanamycin exhibited anticancer and pro-apoptotic activity in gastric cancer and cholangiocarcinoma cells, as s single agent or in combination with NVP-AUY922. Consistently, HSP90 inhibition by LD053 induced the inhibition of the pro-survival signaling pathway (i.e., c-RAF/MEK/ERK or PI3K/AKT) in gastric cancer cells [163]. However, in spite of this strong rationale, until now, HSP90 inhibitors failed to keep their promise in a clinical setting, and demonstrated several limitations either in terms of efficacy due to the incomplete inhibition of HSP90 [164], or in terms of toxicity.…”

Section: Conclusion: the Metabolism/epigenetic Bidirectional Crosmentioning

confidence: 87%

HSP90 Molecular Chaperones, Metabolic Rewiring, and Epigenetics: Impact on Tumor Progression and Perspective for Anticancer Therapy

Condelli

Crispo

Pietrafesa

et al. 2019

Cells

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Heat shock protein 90 (HSP90) molecular chaperones are a family of ubiquitous proteins participating in several cellular functions through the regulation of folding and/or assembly of large multiprotein complexes and client proteins. Thus, HSP90s chaperones are, directly or indirectly, master regulators of a variety of cellular processes, such as adaptation to stress, cell proliferation, motility, angiogenesis, and signal transduction. In recent years, it has been proposed that HSP90s play a crucial role in carcinogenesis as regulators of genotype-to-phenotype interplay. Indeed, HSP90 chaperones control metabolic rewiring, a hallmark of cancer cells, and influence the transcription of several of the key-genes responsible for tumorigenesis and cancer progression, through either direct binding to chromatin or through the quality control of transcription factors and epigenetic effectors. In this review, we will revise evidence suggesting how this interplay between epigenetics and metabolism may affect oncogenesis. We will examine the effect of metabolic rewiring on the accumulation of specific metabolites, and the changes in the availability of epigenetic co-factors and how this process can be controlled by HSP90 molecular chaperones. Understanding deeply the relationship between epigenetic and metabolism could disclose novel therapeutic scenarios that may lead to improvements in cancer treatment.

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Section: Conclusion: the Metabolism/epigenetic Bidirectional Crosmentioning

confidence: 87%

HSP90 Molecular Chaperones, Metabolic Rewiring, and Epigenetics: Impact on Tumor Progression and Perspective for Anticancer Therapy

Condelli

Crispo

Pietrafesa

et al. 2019

Cells

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show abstract

“…[16] In this case, the Hsp90 level was elevated, consistent with the role of Hsp90 playing an essential role in cancer and being also correlated with poor prognosis in cancer. [17][18][19] To some extent, it seems that AAM possesses potentially malignant or a tendency of regrowth. At gene expression level, AAM has a positive expression of vimentin, SMA, MSA, desmin, CD34, F8, ER, PR, [20] and negative expression for S-100, CK, and CD68.…”

Section: Discussionmentioning

confidence: 99%

A giant aggressive angiomyxoma of vulva in a young woman

2019

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Rationale:Aggressive angiomyxoma (AAM) is a rare and benign invasive mesenchymal stromal tumor predominantly in women at reproductive age. AAM tends to relapse locally and should be differentially diagnosed from other mesenchymal tumors.Patient concerns:We report here a rare case of massive vulvar AAM in a 22-year-old Chinese woman with left labia majora mass with ulcer.Diagnoses:The diagnosis “aggressive angiomyxoma of vulva” was based on clinicopathologic and immunohistochemical features.Interventions:A surgery with local excision of the mass was performed.Outcomes:The patient was discharged 12 days after the surgery. There was no AAM recurrence or metastasis in a period of 12-month follow-up.Lessons:The vulvar AAM is a benign and aggressive mesenchymal tumor. In this case, we present the diagnosis, treatment, and prognosis for vulvar AAM. The tumor was removed completely by the surgery, but a long-term follow-up is requisite for surveilling on recurrence.

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“…Altered cellular energy metabolism, in particular aerobic glycolysis (the Warburg effect), is a hallmark of cancer but also of severe angioproliferative PAH (5,16,18,43,134,196). Glycolysis is controlled, among others, by p53, the oncogene cMyc and HIF (Fig.…”

Section: Phenotype Switch and Endothelial Cell Mesenchymal Transitionmentioning

confidence: 99%

The hallmarks of severe pulmonary arterial hypertension: the cancer hypothesis—ten years later

Kuebler

Bogaard

Spiekerkoetter

et al. 2020

American Journal of Physiology-Lung Cellular and Molecular Phys

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Severe forms of pulmonary arterial hypertension (PAH) are most frequently the consequence of a lumen-obliterating angiopathy. One pathobiological model is that the initial pulmonary vascular endothelial cell injury and apoptosis is followed by the evolution of phenotypically altered, apoptosis-resistant, proliferating cells and an inflammatory vascular immune response. Although there may be a vasoconstrictive disease component, the increased pulmonary vascular shear stress in established PAH is caused largely by the vascular wall pathology. In this review, we revisit the “quasi-malignancy concept” of severe PAH and examine to what extent the hallmarks of PAH can be compared with the hallmarks of cancer. The cancer model of severe PAH, based on the growth of abnormal vascular and bone marrow-derived cells, may enable the emergence of novel cell-based PAH treatment strategies.

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Therapeutic potency of heat-shock protein-90 pharmacological inhibitors in the treatment of gastrointestinal cancer, current status and perspectives

Cited by 15 publications

References 55 publications

HSP90 Molecular Chaperones, Metabolic Rewiring, and Epigenetics: Impact on Tumor Progression and Perspective for Anticancer Therapy

HSP90 Molecular Chaperones, Metabolic Rewiring, and Epigenetics: Impact on Tumor Progression and Perspective for Anticancer Therapy

A giant aggressive angiomyxoma of vulva in a young woman

The hallmarks of severe pulmonary arterial hypertension: the cancer hypothesis—ten years later

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