Evolution of ramucirumab in the treatment of cancer – A review of literature

Abstract

Ramucirumab is a recombinant human monoclonal antibody and is used in the treatment of advanced malignancies. Its mechanism of action is by inhibiting angiogenesis in tumor cells by targeting the vascular endothelial growth factor receptor 2. United States Food and Drug Administration (FDA) approved it initially in 2014 for the treatment of advanced gastric or gastro-esophageal junction adenocarcinoma and metastatic non-small cell lung carcinoma. It was approved by FDA in 2015 for the treatment of advanced colorectal cancer. This manuscript consolidates pre-clinical trials to phase I, II, and III trial data indicating the effects of ramucirumab on different cancer types, which led to its approval. By comparing these clinical trials alongside each other, we can more easily examine the studies that have already been completed, along with currently ongoing studies and potential further areas of interest for this newly approved treatment. This approach makes it convenient to compare dosages, overall survival, adverse events, as well as possible routes for combination therapy with ramucirumab. By compiling results for various oncological malignancies, we can differentiate between treatments that are effective and have the highest incidence of stable disease, and those that do not seem promising. Ramucirumab has been effective in the treatment of various carcinomas and this article outlines other tumors in which this treatment option may be successful.

Site-Specific N-Glycosylation of Endothelial Cell Receptor Tyrosine Kinase VEGFR-2

“…Ramucirumab, a monoclonal antibody, targets the extracellular domain of VEGFR-2, while other therapeutic agents such as bevacizumab (Avastin) and Sorafenib target the VEGF-A ligand or the intracellular kinase domain of the receptor, respectively. 27 Despite evidence of promising clinical responses to anti-angiogenesis drugs, their successes are restricted by insufficient efficacy and development of refractory tumors and resistance. 28 Understanding the N -glycosylation of VEGFR-2 may offer insight into the role of N -linked glycans in VEGFR-2 function and possible links between insufficient efficacy and refractoriness of anti-angiogenesis therapeutics.…”

Remodeling of the Extracellular Matrix by Endothelial Cell-Targeting siRNA Improves the EPR-Based Delivery of 100 nm Particles

“…27,28 The relationship, however, between VEGFR2 and ECMs in the tumor tissue is not well validated. On the other hand, abundant ECMs are a typical symptom for fibrotic diseases in noncancerous tissues, such as cirrhosis of the liver.…”

Gastric cancer management: Kinases as a target therapy

“…The prospects of targeted therapy as a promising new tool in the therapeutic arsenal of GC were further supported by the approval of ramucirumab by the FDA in 2014 as a second‐line treatment alone or in combination with paclitaxel for patients with local relapse or metastatic gastric cancer . Ramucirumab is a fully humanized monoclonal antibody that antagonizes vascular endothelial growth factor (VEGFR)‐2 and inhibits angiogenesis in tumour cells . The inclusion of ramucirumab was based on the positive results of the phase III REGARD and phase III RAINBOW trials, which demonstrated improved median PFS and overall survival (OS) benefits.…”

“…36 Ramucirumab is a fully humanized monoclonal antibody that antagonizes vascular endothelial growth factor (VEGFR)-2 and inhibits angiogenesis in tumour cells. 37 The inclusion of ramucirumab was based on the positive results of the phase III REGARD 38 and phase III RAINBOW trials, 39 which demonstrated improved median PFS and overall survival (OS) benefits.…”