VEGF inhibition in urothelial cancer: the past, present and future

Ghafouri, Sanaz N.; Burkenroad, Aaron; Pantuck, Morgan; Almomani, Bara; Stefanoudakis, Dimitris; Shen, John; Drakaki, Alexandra

doi:10.1007/s00345-020-03213-z

Cited by 16 publications

(9 citation statements)

References 49 publications

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“…Our study did not show a significant increase in treatment-related grade ≥ 3 adverse events in patients receiving ramucirumab, compared to another anti-VEGF agent bevacizumab, which showed a statistically significant increase in occurrence of deep vein thrombosis and pulmonary embolism [6]. This is particularly important given that the median age at diagnosis of patients with bladder cancer is 73 years [4]; therefore, there are many concomitant medical conditions in these individuals that make treatment of this disease challenging.…”

Section: Discussioncontrasting

confidence: 71%

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Ramucirumab as a Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: A Meta-Analysis of Randomized Clinical Trials

Ilić

Ilic

2021

The 1st International Electronic Conference on Biomedicine

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Improvement of treatment outcomes in patients with locally advanced or metastatic urothelial carcinoma represents an important unmet need, since survival remains poor in patients who progress beyond first-line treatment. The purpose of this study was to investigate the effects of ramucirumab, a human monoclonal antibody that binds to VEGFR-2, in the treatment of locally advanced or metastatic urothelial carcinoma. A literature search of PubMed and CENTRAL was conducted. Outcomes of interest were overall survival (OS), progression-free survival (PFS) and the rate of adverse events. Time-to-event outcomes were combined using the generic inverse-variance method and presented as hazard ratio (HR) with 95% confidence intervals (95% CI), while dichotomous events were combined using the Mantel–Haenszel method and presented as odds ratio (OR) with 95% CI. All of the analyses were performed in RevMan 5.3. The literature search identified two randomized controlled trials. The addition of ramucirumab to docetaxel resulted in a statistically significant improvement in PFS (HR = 0.55, 95% CI 0.31–0.96, p = 0.030), while the difference was not significant for OS (HR = 0.86, 95%CI 0.71–1.04, p = 0.12). Subgroup analysis by sex, age (<65 and ≥65 years), baseline hemoglobin (<10 g/dL and ≥10 g/dL), presence of visceral metastases and presence of liver metastases did not identify a subgroup in which improvement in OS was present. The difference in treatment-related grade ≥ 3 adverse events was not significant (OR = 1.47, 95%CI 0.95–2.27, p = 0.08). Ramucirumab in addition to docetaxel significantly improved PFS in patients with locally advanced or metastatic urothelial carcinoma. Future studies are necessary to identify a subset of patients who might experience a significant improvement in OS.

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Section: Discussioncontrasting

confidence: 71%

“…Ramucirumab is an IgG1 human monoclonal antibody that binds to the vascular endothelial growth factor receptor 2 (VEGFR-2) and inhibits the VEGF pathway [5]. Research shows a promising role for VEGF-inhibitors in a population of patients with platinumrefractory advanced urothelial carcinoma [6].…”

Section: Introductionmentioning

confidence: 99%

Ramucirumab as a Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: A Meta-Analysis of Randomized Clinical Trials

Ilić

Ilic

2021

The 1st International Electronic Conference on Biomedicine

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“…VEGF has been suggested to plays a role in immunomodulation [53]. Moreover, anti-angiogenic therapy is a promising strategy against urothelial cancer initiation and progression [54]. Our study found no relationship between HLA or VEGF plasma levels and clinicopathological features.…”

Section: Discussioncontrasting

confidence: 46%

Genetic contributions of MHC class I antigen processing and presentation pathway to bladder cancer risk and recurrence

Wieczorek¹,

Jabłonowski²,

Lesicka³

et al. 2022

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Human leukocyte antigen class I (HLA class I) antigen processing and presentation pathway (APP) defines anticontrol HLA class I expression in the tumor and the repertoire of presented tumor antigens. At the same time, vascular endothelial growth factor (VEGF) acts as an immunomodulator in the tumor microenvironment. The objective of the current study was to examine the association of single nucleotide polymorphisms (SNPs) in the ERAP1, ERAP2, TAP1, TAP2, TAPBP, IFNG genes with the corresponding mRNA expression in bladder cancer (BC) risk and recurrence after transurethral resection of BC. Moreover, we assessed the relationship between HLA class I and VEGF plasma levels and BC recurrence. We analyzed nine SNPs in 124 BC patients using TaqMan genotyping and compared them with the data from 503 healthy individuals from the 1000 Genomes Project. In addition, we quantified the effects of SNPs on the corresponding mRNA expression in tumor and non-tumor adjacent tissue in 60 BC patients with primary and 30 with recurrent tumor by quantitative real-time PCR. Furthermore, the plasma HLA class I and VEGF levels were analyzed in BC patients and healthy controls by ELISA. IFNG (rs1861493) was associated with BC risk, TAPBP (rs3106189, rs2071888) with recurrence-free survival (RFS). Moreover, TAPBP mRNA expression was lower in tumors than in the adjacent tissue. The SNPs ERAP2 (rs251339) and TAP2 (rs241447, rs241448) variants affected mRNA expression in BC tissue. In tumor tissue, the high mRNA expression of ERAP1 was more common in BC patients with single tumors, ERAP2 in nonsmokers, and TAP2 mRNA in recurrence. The lower HLA and higher VEGF plasma levels were observed in BC patients compared with healthy controls. We conclude that the genetic elements responsible for MHC class I APP may influence the BC risk, risk of recurrence, and RFS.

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“…VEGF and bFGF are important tumor angiogenesis promoters. VEGF is the hub connecting various networks of neovascularization, and it is also the most powerful and specific stimulator of vascular endothelial cell proliferation found so far and is closely related to the growth, metastasis, and prognosis of various tumors [ 21 , 22 ]. bFGF is another important proangiogenic growth factor produced by tumor cells and macrophages, and it is also the first proangiogenic growth factor to be identified.…”

Section: Discussionmentioning

confidence: 99%

The Protective Mechanism of Afuresertib against Esophageal Cancer

et al. 2022

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Esophageal cancer (EC) is a common malignant tumor of the digestive system. Exploring the molecular biological mechanism of EC will help to clarify its carcinogenesis mechanism, find important molecular targets in the process of carcinogenesis, and provide new ideas for the diagnosis and treatment of EC. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the signal transduction pathways most closely related to cell proliferation and apoptosis. The regulation of various downstream molecules affects the proliferation and growth of tumor cells. In this study, we determined the effect of different concentrations of afuresertib on cell viability by MTT assay and determined the effect of afuresertib on cell apoptosis by Annexin V-FITC/PI dual staining. Animal experiments verified the effects of afuresertib on VEGF, bFGF, and PI3K/Akt. Our results indicated that afuresertib is closely related to the survival, proliferation, and apoptosis of esophageal cancer cell lines. More importantly, we found that afuresertib could reduce tumor volume and mass in EC rats through in vivo experiments. In conclusion, afuresertib may exert its antitumor effect by inhibiting the expression of PI3K and Akt-related proteins in rat tumor tissues.

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VEGF inhibition in urothelial cancer: the past, present and future

Cited by 16 publications

References 49 publications

Ramucirumab as a Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: A Meta-Analysis of Randomized Clinical Trials

Ramucirumab as a Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: A Meta-Analysis of Randomized Clinical Trials

Genetic contributions of MHC class I antigen processing and presentation pathway to bladder cancer risk and recurrence

The Protective Mechanism of Afuresertib against Esophageal Cancer

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