Clinical Evaluation of Ramucirumab for the Treatment of Hepatocellular Carcinoma (HCC): Place in Therapy

Choucair, Khalil; Kamran, Syed; Saeed, Anwaar

doi:10.2147/ott.s268309

Cited by 7 publications

(6 citation statements)

References 64 publications

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“…To date, targeted therapy drugs represented by sorafenib have dominated drug treatment in advanced HCC for many years. In the past 5 years, a variety of internationally recognized targeted drugs have emerged, such as lenvatinib, cabozantinib, regorafenib and ramucirumab 39–42 . Although the diversity of medicines has increased, other treatment options are lacking when targeted therapy fails.…”

Section: Discussionmentioning

confidence: 99%

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Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma

Song

Cai

et al. 2023

J Cellular Molecular Medi

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Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths among cancer patients. Vascular endothelial growth factor A (VEGFA) is involved in regulating biological processes, such as angiogenesis and vascular permeability, and is very closely related to the pathogenesis of various tumours, especially vascular-rich, solid tumours. Clinical data of patients with HCC and other tumours were analysed through public databases, such as the TCGA database, Gene Expression Omnibus database, Human Protein Atlas database, STRING, Tumour Immune Estimation Resource and Kaplan-Meier Plotter. The tumour tissues and adjacent normal tissues of patients with HCC from Hunan Provincial People's Hospital were collected to verify the expression of VEGFA by immunohistochemistry, immunofluorescence, Western blotting and qPCR. VEGFA expression is elevated in multiple tumour types and correlates with the prognosis of tumour patients. VEGFA is involved in regulating the tumour microenvironment and immune cell function in tumour development. Inhibition of VEGFA reduces proliferation, invasion, and migration and promotes apoptosis in HCC cells.VEGFA is a potential predictive biomarker for the diagnosis and prognosis of HCC.

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Section: Discussionmentioning

confidence: 99%

“…In the past 5 years, a variety of internationally recognized targeted drugs have emerged, such as lenvatinib, cabozantinib, regorafenib and ramucirumab. 39 , 40 , 41 , 42 Although the diversity of medicines has increased, other treatment options are lacking when targeted therapy fails.…”

Section: Discussionmentioning

confidence: 99%

Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma

Song

Cai

et al. 2023

J Cellular Molecular Medi

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“…In a pooled analysis between these trials, treatment-related adverse events commonly seen with Ramucirumab were mostly mild to moderate, which included peripheral edema, anorexia, nausea, fatigue, diarrhea, abdominal pain, and headache. Treatment emergent adverse reactions included hypertension and hyponatremia [ 42 ].…”

Section: Second-line Treatmentsmentioning

confidence: 99%

“…Additionally, three patients expired from drug-related complications including acute kidney injury, hepato-renal syndrome, and renal failure. Overall, in comparison to first-line agents such as Sorafenib, the toxicity profile for Ramucirumab was shown to be more favorable [ 42 ]. REACH-2 concluded that in HCC patients with AFP 400 ng/mL or more, there is an increased survival benefit and reduced risk of death (29%) [ 40 ].…”

Section: Second-line Treatmentsmentioning

confidence: 99%

A Review of Current and Emerging Therapies for Advanced Hepatocellular Carcinoma

et al. 2022

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Hepatocellular carcinoma remains a leading cause of cancer-related deaths worldwide. Liver disease including cirrhosis and viral hepatitis remains among the leading causes of hepatocellular carcinoma and despite increased screening, many patients are diagnosed in the advanced stages precluding them from locoregional therapy. Therapeutic agents for advanced hepatocellular carcinoma were limited to Sorafenib for several years; however, with the emergence of molecular targeted therapies including tyrosine kinase inhibitors and vascular endothelial growth factor inhibitors, in addition to immunotherapies, the way hepatocellular carcinoma is treated has changed significantly. In this review, we summarize the key clinical trials that lead to the approval of these agents for systemic treatment of hepatocellular carcinoma and discuss the preferred sequence of treatment options as well as prospective studies for management of hepatocellular carcinoma.

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“…Ramucirumab, a VEGFR2-targeted monoclonal antibody, and several VEGFR small molecule inhibitors have been approved for clinical use [ 2 , 9 ]. However, ramucirumab has been associated with limited efficacy, potentially severe side effects, and high cost [ 10 , 11 ]. Similarly, currently available small molecules have been associated with acquired drug resistance, limited efficacy, compound toxicity, and a wide range of side effects [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative biochemical kinase activity analysis identifies rivoceranib as a highly selective VEGFR2 inhibitor

Jang¹,

Strickland²,

Finis³

et al. 2023

Cancer Chemother Pharmacol

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Vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis, is highly expressed across numerous tumor types and has been an attractive target for anti-cancer therapy. However, clinical application of available VEGFR2 inhibitors has been challenged by limited efficacy and a wide range of side effects, potentially due to inadequate selectivity for VEGFR2. Thus, development of potent VEGFR2 inhibitors with improved selectivity is needed. Rivoceranib is an orally administered tyrosine kinase inhibitor that potently and selectively targets VEGFR2. A comparative understanding of the potency and selectivity of rivoceranib and approved inhibitors of VEGFR2 is valuable to inform rationale for therapy selection in the clinic. Here, we performed biochemical analyses of the kinase activity of VEGFR2 and of a panel of 270 kinases to compare rivoceranib to 10 FDA-approved kinase inhibitors (“reference inhibitors”) with known activity against VEGFR2. Rivoceranib demonstrated potency within the range of the reference inhibitors, with a VEGFR2 kinase inhibition IC50 value of 16 nM. However, analysis of residual kinase activity of the panel of 270 kinases showed that rivoceranib displayed greater selectivity for VEGFR2 compared with the reference inhibitors. Differences in selectivity among compounds within the observed range of potency of VEGFR2 kinase inhibition are clinically relevant, as toxicities associated with available VEGFR2 inhibitors are thought to be partly due to their effects against kinases other than VEGFR2. Together, this comparative biochemical analysis highlights the potential for rivoceranib to address clinical limitations associated with off-target effects of currently available VEGFR2 inhibitors.

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Clinical Evaluation of Ramucirumab for the Treatment of Hepatocellular Carcinoma (HCC): Place in Therapy

Cited by 7 publications

References 64 publications

Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma

Vascular endothelial growth factor A is a potential prognostic biomarker and correlates with immune cell infiltration in hepatocellular carcinoma

A Review of Current and Emerging Therapies for Advanced Hepatocellular Carcinoma

Comparative biochemical kinase activity analysis identifies rivoceranib as a highly selective VEGFR2 inhibitor

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