An updated patent review of VEGFR-2 inhibitors (2017-present)

Farghaly, Thoraya A.; Al-Hasani, Wedian A.; Abdulwahab, Hanan Gaber

doi:10.1080/13543776.2021.1935872

Cited by 39 publications

(17 citation statements)

References 31 publications

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“…The results suggested that the expression of VEGFR-2 in the primary tumors of WDLPS and DDLPS with PS was higher than that in tumors without PS, especially in DDLPS (P = 0.020). In the VEGFR family, VEGFR-2 is considered as the most critical factor to promote angiogenesis ( 33 ). Studies have shown that tyrosine kinase inhibitors targeting VEGFR-2 could inhibit tumor angiogenesis and tumor growth ( 34 , 35 ), and could also directly induce autophagy and apoptosis of tumor cells ( 36 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

Multidimensional characteristics, prognostic role, and preoperative prediction of peritoneal sarcomatosis in retroperitoneal sarcoma

et al. 2022

Front. Oncol.

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BackgroundPeritoneal sarcomatosis (PS) could occur in patients with retroperitoneal sarcomas (RPS). This study aimed to expand the understanding of PS on its characteristics and prognostic role, and develop a nomogram to predict its occurrence preoperatively.MethodsData of 211 consecutive patients with RPS who underwent surgical treatment between 2011 and 2019 was retrospectively reviewed. First, the clinicopathological characteristics of PS were summarized and analyzed. Second, the disease-specific survival (DSS) and recurrence-free survival (RFS) of patients were analyzed to evaluate the prognostic role of PS. Third, preoperative imaging, nearly the only way to detect PS preoperatively, was combined with other screened risk factors to develop a nomogram. The performance of the nomogram was assessed.ResultsAmong the 211 patients, 49 (23.2%) patients had PS with an incidence of 13.0% in the primary patients and 35.4% in the recurrent patients. The highest incidence of PS occurred in dedifferentiated liposarcoma (25.3%) and undifferentiated pleomorphic sarcoma (25.0%). The diagnostic sensitivity of the preoperative imaging was 71.4% and its specificity was 92.6%. The maximum standardized uptake value (SUVmax) was elevated in patients with PS (P<0.001). IHC staining for liposarcoma revealed that the expression of VEGFR-2 was significantly higher in the PS group than that in the non-PS group (P = 0.008). Survival analysis (n =196) showed significantly worse DSS in the PS group than in non-PS group (median: 16.0 months vs. not reached, P < 0.001). In addition, PS was proven as one of the most significant prognostic predictors of both DSS and RFS by random survival forest algorithm. A nomogram to predict PS status was developed based on preoperative imaging combined with four risk factors including the presentation status (primary vs. recurrent), ascites, SUVmax, and tumor size. The nomogram significantly improved the diagnostic sensitivity compared to preoperative imaging alone (44/49, 89.8% vs. 35/49, 71.4%). The C-statistics of the nomogram was 0.932, and similar C-statistics (0.886) was achieved at internal cross-validation.ConclusionPS is a significant prognostic indicator for RPS, and it occurs more often in recurrent RPS and in RPS with higher malignant tendency. The proposed nomogram is effective to predict PS preoperatively.

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Section: Discussionmentioning

confidence: 99%

Multidimensional characteristics, prognostic role, and preoperative prediction of peritoneal sarcomatosis in retroperitoneal sarcoma

et al. 2022

Front. Oncol.

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“…The role of VEGF depends on the activation of its receptor. The activation of VEGFR-1 leads to inflammation, while the activation of VEGFR-2 leads to angiogenesis (Farghaly et al, 2021). It was found that the abnormal pattern of VEGF receptor, the decrease of VEGF's mRNA level, the increase of VEGFR-1 level and the decrease of VEGFR-2 level are the essential reasons for the failure of wound healing (Zhou et al, 2015).…”

Section: Defects In the Number And Type Of Growth Factorsmentioning

confidence: 99%

Oxidative Stress and Lipid Peroxidation: Prospective Associations Between Ferroptosis and Delayed Wound Healing in Diabetic Ulcers

Feng

Wang

et al. 2022

Front. Cell Dev. Biol.

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Diabetic ulcers are one of the major complications of diabetes, and patients usually suffer from amputation and death due to delayed ulcer wound healing. Persistent inflammation and oxidative stress at the wound site are the main manifestations of delayed wound healing in diabetic ulcers. In addition, chronic hyperglycemia in patients can lead to circulatory accumulation of lipid peroxidation products and impaired iron metabolism pathways leading to the presence of multiple free irons in plasma. Ferroptosis, a newly discovered form of cell death, is characterized by intracellular iron overload and accumulation of iron-dependent lipid peroxides. These indicate that ferroptosis is one of the potential mechanisms of delayed wound healing in diabetic ulcers and will hopefully be a novel therapeutic target for delayed wound healing in diabetic patients. This review explored the pathogenesis of diabetic ulcer wound healing, reveals that oxidative stress and lipid peroxidation are common pathological mechanisms of ferroptosis and delayed wound healing in diabetic ulcers. Based on strong evidence, it is speculated that ferroptosis and diabetic ulcers are closely related, and have value of in-depth research. We attempted to clarify prospective associations between ferroptosis and diabetic ulcers in terms of GPX4, iron overload, ferroptosis inhibitors, AGEs, and HO-1, to provide new ideas for exploring the clinical treatment of diabetic ulcers.

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“…It is potentially a therapeutic approach for angiogenesis‐related diseases, Alzheimer's disease, Parkinson's disease, and cancer. Hence, numerous VEGFR‐2 inhibitors have been clinically tested and/or validated for the therapeutic use in angiogenesis‐related diseases 76,152 . Brivanib, a selective dual‐RTK inhibitor, inhibits FGFR and VEGFRs.…”

Section: Kinase Groupsmentioning

confidence: 99%

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

Pang

Wang

Qin

et al. 2022

MedComm

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Protein phosphorylation is an important post‐transcriptional modification involving an extremely wide range of intracellular signaling transduction pathways, making it an important therapeutic target for disease intervention. At present, numerous drugs targeting protein phosphorylation have been developed for the treatment of various diseases including malignant tumors, neurological diseases, infectious diseases, and immune diseases. In this review article, we analyzed 303 small‐molecule protein phosphorylation kinase inhibitors (PKIs) registered and participated in clinical research obtained in a database named Protein Kinase Inhibitor Database (PKIDB), including 68 drugs approved by the Food and Drug Administration of the United States. Based on previous classifications of kinases, we divided these human protein phosphorylation kinases into eight groups and nearly 50 families, and delineated their main regulatory pathways, upstream and downstream targets. These groups include: protein kinase A, G, and C (AGC) and receptor guanylate cyclase (RGC) group, calmodulin‐dependent protein kinase (CaMK) group, CMGC [Cyclin‐dependent kinases (CDKs), Mitogen‐activated protein kinases (MAPKs), Glycogen synthase kinases (GSKs), and C dc2‐like kinases (CLKs)] group, sterile (STE)‐MAPKs group, tyrosine kinases (TK) group, tyrosine kinase‐like (TKL) group, atypical group, and other groups. Different groups and families of inhibitors stimulate or inhibit others, forming an intricate molecular signaling regulatory network. This review takes newly developed new PKIs as breakthrough point, aiming to clarify the regulatory network and relationship of each pathway, as well as their roles in disease intervention, and provide a direction for future drug development.

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An updated patent review of VEGFR-2 inhibitors (2017-present)

Cited by 39 publications

References 31 publications

Multidimensional characteristics, prognostic role, and preoperative prediction of peritoneal sarcomatosis in retroperitoneal sarcoma

Multidimensional characteristics, prognostic role, and preoperative prediction of peritoneal sarcomatosis in retroperitoneal sarcoma

Oxidative Stress and Lipid Peroxidation: Prospective Associations Between Ferroptosis and Delayed Wound Healing in Diabetic Ulcers

Role of protein phosphorylation in cell signaling, disease, and the intervention therapy

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