Novel Drugs with High Efficacy against Tumor Angiogenesis

Qi, Shaohua; Deng, Shoulong; Lian, Zhengxing; Yu, Kun

doi:10.3390/ijms23136934

Cited by 43 publications

(39 citation statements)

References 229 publications

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“…Indeed, Sorafenib, a potent kinase inhibitor and anti-cancer molecule, seems to sequester YAP, thereby facilitating formation of the SRF/MYOCD complex and expression of VSMC-specific contractile genes ( Huang et al, 2019 ). However, Sorafenib is a non-specific inhibitor of growth factor receptors known to impair EC proliferation and tumoral angiogenesis ( Liu et al, 2006 ; Qi et al, 2022 ), which may impair endothelium repair and prolong the need for anti-thrombotic similarly to paclitaxel and Sirolimus.…”

Section: Treatment Of Intimal Hyperplasiamentioning

confidence: 99%

Vascular smooth muscle cells in intimal hyperplasia, an update

2023

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Arterial occlusive disease is the leading cause of death in Western countries. Core contemporary therapies for this disease include angioplasties, stents, endarterectomies and bypass surgery. However, these treatments suffer from high failure rates due to re-occlusive vascular wall adaptations and restenosis. Restenosis following vascular surgery is largely due to intimal hyperplasia. Intimal hyperplasia develops in response to vessel injury, leading to inflammation, vascular smooth muscle cells dedifferentiation, migration, proliferation and secretion of extra-cellular matrix into the vessel’s innermost layer or intima. In this review, we describe the current state of knowledge on the origin and mechanisms underlying the dysregulated proliferation of vascular smooth muscle cells in intimal hyperplasia, and we present the new avenues of research targeting VSMC phenotype and proliferation.

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Section: Treatment Of Intimal Hyperplasiamentioning

confidence: 99%

Vascular smooth muscle cells in intimal hyperplasia, an update

2023

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“…However, the secretory pathway or mechanism in cardiovascular disease needs further study. Studies have shown that HSP90 mediates AngII-induced vascular smooth muscle cell (VSMC) proliferation and remodeling, and brain microvascular injury during hypertension [ 20 , 72 , 73 ]. Adventitial remodeling is involved in the evolution of several vascular diseases including hypertension [ 74 ].…”

Section: Hsp90 and Cardiovascular Diseasementioning

confidence: 99%

“…HSP90 can be thought of as a “molecular buffer” that maintains the general balance and fidelity of cell signaling, and HSP90 inhibitors are being investigated for the treatment of various conditions [ 16 ]. In addition to their development in cancer therapy, HSP90 inhibitors have important roles in the treatment of many inflammatory diseases [ 6 , 7 , 17 , 18 , 19 , 20 ]. At the same time, they can be used as a target for the treatment of cardiovascular disease (CVD) [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of HSP90 Inhibitors in the Treatment of Cardiovascular Diseases

et al. 2022

Cells

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Cardiovascular disease is the result of complicated pathophysiological processes in the tissues that make up the blood vessels and heart. Heat shock protein 90 (HSP90) can interact with 10% of the proteome and is the most widely studied molecular chaperone in recent years. HSP90 is extensively involved in the regulation of protein folding and intracellular protein stability, making HSP90 a hopeful target for the treatment of multiple cardiovascular diseases. Numerous client proteins of HSP90 have been identified in known cardiac disease pathways, including MAPK signaling, PI3K/AKT (PKB)/mTOR, and TNF-α signaling. Therefore, these pathways can be controlled by regulating HSP90. Among them, the activity of HSP90 can be regulated via numerous inhibitors. In this review, first, we will discuss the function of HSP90 and its role in pathological pathways. In addition, HSP90 plays a significant role in most cardiovascular diseases, including hypertension, pulmonary venous hypertension, atherosclerosis, and heart failure; next we will focus on this part. Finally, we will summarize the currently known HSP90 inhibitors and their potential in the treatment of heart disease.

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“…Other effects of HSPs that could be employed for the development of anti-cancer therapies is their potential antiangiogenic properties which were reported by several studies [ 39 , 40 , 41 , 42 ]. HSP90 inhibitors exert antiangiogenic effects by affecting the PI-3K/AKT and eNOS signal transduction pathways in endothelial cells [ 43 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

Babi¹,

Menlibayeva²,

Bex³

et al. 2022

Cancers

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Heat shock proteins (HSPs) are conservative and ubiquitous proteins that are expressed both in prokaryotic and eukaryotic organisms and play an important role in cellular homeostasis, including the regulation of proteostasis, apoptosis, autophagy, maintenance of signal pathways, protection from various stresses (e.g., hypoxia, ionizing radiation, etc.). Therefore, HSPs are highly expressed in tumor cells, including malignant brain tumors, where they also associate with cancer cell invasion, metastasis, and resistance to radiochemotherapy. In the current review, we aimed to assess the diagnostic and prognostic values of HSPs expression in CNS malignancies as well as the novel treatment approaches to modulate the chaperone levels through the application of inhibitors (as monotherapy or in combination with other treatment modalities). Indeed, for several proteins (i.e., HSP10, HSPB1, DNAJC10, HSPA7, HSP90), a direct correlation between the protein level expression and poor overall survival prognosis for patients was demonstrated that provides a possibility to employ them as prognostic markers in neuro-oncology. Although small molecular inhibitors for HSPs, particularly for HSP27, HSP70, and HSP90 families, were studied in various solid and hematological malignancies demonstrating therapeutic potential, still their potential was not yet fully explored in CNS tumors. Some newly synthesized agents (e.g., HSP40/DNAJ inhibitors) have not yet been evaluated in GBM. Nevertheless, reported preclinical studies provide evidence and rationale for the application of HSPs inhibitors for targeting brain tumors.

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Novel Drugs with High Efficacy against Tumor Angiogenesis

Cited by 43 publications

References 229 publications

Vascular smooth muscle cells in intimal hyperplasia, an update

Vascular smooth muscle cells in intimal hyperplasia, an update

The Role of HSP90 Inhibitors in the Treatment of Cardiovascular Diseases

Targeting Heat Shock Proteins in Malignant Brain Tumors: From Basic Research to Clinical Trials

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