Ramucirumab: A Novel Antiangiogenic Agent

Wadhwa, Roopma; Takenaka, Takashi; Sudo, Kazuki; Blum-Murphy, Mariela; Ajani, Jaffer A.

doi:10.2217/fon.13.68

Cited by 30 publications

(21 citation statements)

References 20 publications

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“…The comprehensive treatment based on fluorouracil containing chemotherapy is the main strategy for AGC. Although the addition of targeted drugs (trastuzumab, apatinib, and ramucirumab) 2 3 4 has improved the prognosis to some extent in recent years, the clinical outcome of AGC is not satisfactory due to the fewer therapeutic drugs and frequent drug resistance resulting from high heterogeneity and other mechanisms. As a consequence, developing new drugs and exploring the mechanisms of drug resistance are very urgent for AGC.…”

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confidence: 99%

Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer

Zhu

Tian

et al. 2015

Sci Rep

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The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. PDTX models of gastric cancer using surgical tissues are reported occasionally; however, the PDTX models using gastroscopic biopsies, which are best for evaluating new drugs, are unreported. In our study, a total of 185 fresh gastroscopic biopsies of gastric cancer were subcutaneously transplanted into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice. Sixty-three PDTX models were successfully established (34.1%, 63/185) and passaged to maintain tumors in vivo, and the mean latency period of xenografts was 65.86 ± 32.84 days (11–160 days). Biopsies of prior chemotherapy had a higher transplantation rate (52.1%, 37/71) than biopsies after chemotherapy (21.9%, 25/114; P = 0.000). No differences were found between the latency period of xenografts and characteristics of patients. The pathological and molecular features of PDTX as well as chemosensitivity were highly consistent with those of primary tumors of patients. The genetic characteristics were stable during passaging of PDTX models. In summary PDTX models using gastroscopic biopsies in gastric cancer were demonstrated for the first time, and the biological characteristics of the PDTX models were highly consistent with patients, which provided the best preclinical study platform for gastric cancer.

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confidence: 99%

Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer

Zhu

Tian

et al. 2015

Sci Rep

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“…The chemical structure comprises two identical heavy chains of 446 amino acids and two identical light chains of 214 amino acids 18,19. It inhibits angiogenesis by binding specifically to the extracellular domain of VEGFR-2 inhibiting binding of VEGF receptor ligands VEGF-A, VEGF-C, and VEGF-D 18.…”

Section: Chemistry and Actionmentioning

confidence: 99%

Spotlight on ramucirumab in the treatment of nonsmall cell lung cancer: design, development, and clinical activity

Cobo

Gutiérrez

Villatoro

et al. 2017

LCTT

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The vascular endothelial growth factor (VEGF) and receptor is a therapeutic target because of the importance of this pathway in carcinogenesis. This pathway regulates and promotes angiogenesis as well as increases endothelial cell proliferation, permeability, and cancer survival. Ramucirumab is a new fully human monoclonal antibody that targets the VEGF receptor-2, an important key receptor implicated in angiogenesis. Ramucirumab has been approved for the treatment of second-line advanced or metastatic non-small cell lung cancer (NSCLC) in combination with the chemotherapy agent docetaxel. This was based on the result of the randomized trial REVEL of 1,253 patients with metastatic NSCLC previously treated with a platinum-based combination therapy. The authors observed a significant improvement in overall survival (OS) with an acceptable toxicities profile. In this study, patients were randomized to receive ramucirumab plus docetaxel or placebo with docetaxel. The combination of docetaxel and ramucirumab showed an improved OS (hazard ratio [HR]: 0.86; 95% CI: 0.75, 0.98). Median OS was 10.5 months in the ramucirumab arm versus 9.1 months in the placebo arm. Regarding side effects, the toxicity described on the ramucirumab arm were principally diarrhea, fatigue, and neutropenia. The most common (5%) adverse reactions of grade 3 and 4 in the ramucirumab arm were fatigue, neutropenia, febrile neutropenia, leukopenia, and hypertension. Adding ramucirumab to docetaxel improves QoL of patients, and does not impair symptoms or functioning. There are currently several trials in progress evaluating the effects of ramucirumab in combination with other drugs in patients with advanced NSCLC.

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“…A DC101 20 μg/ml koncentrációban megfelelő terápiás hatást mutatott. Az állatkísérletek során a koncentráció-nadír (C min ) nem csökkent a 20 μg/ml érték alá, ezért a klinikai vizsgálatok számára is ezt a célkoncentrációt vá-lasztották [17].…”

Section: Preklinikai Vizsgálatokunclassified

Ramucirumab – egy új gyógyszer az onkológiában

Telekes

Deme²

2016

Orvosi Hetilap

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A ramucirumab egy humanizált vascularis endothelialis növekedési faktor receptor-2 elleni monoklonális antitest, amely megakadályozza a vascularis endothelialis növekedési faktor-A, -C és -D ligandok kötődését. Gátolja továbbá a p44/p42 mitogén aktiválta proteinkinázok ligand által stimulált aktivációját, ezzel neutralizálva a humán endothelsejtek ligand által indukált proliferációját és migrációját. A REGARD (Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma) és a RAINBOW (Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma) vizsgálatok eredményei alapján a ramucirumab befogadásra került másodvonalbeli kezelésként, mint monoterápia és paclitaxellel történő kombinációban a lokálisan recidiváló és nem reszekábilis vagy metasztatizá-ló gyomorrákban (beleértve a gastrooesophagealis junctio adenocarcinomáját is). Az eddigi adatok alapján előrehala-dott szolid daganatokban szenvedő betegeknél a progressziómentes túlélést és a teljes túlélést megnyújthatja a ramucirumab adása, de emellett az összes nemkívánatos esemény kockázatát is megemelheti (fáradtság, neutropenia, vérzés, hányinger, stomatitis). A szerzők áttekintik a ramucirumabbal végzett vizsgálatokat. Orv. Hetil., 2016, 157(40), 1587-1594. Kulcsszavak: ramucirumab, humanizált monoklonális antitest, gyomorrák, szolid daganatok Ramucirumab -a new anticancer agentRamucirumab is a humanized monoclonal antibody against vascular endothelial growth factor receptor-2, which inhibits the binding of vascular endothelial growth factor-A, -C and -D ligands. Furthermore it blocks the ligand stimulated activation of p44/p42 mitogen activated protein kinases, thus neutralizing the ligand induced proliferation and migration of human endothelial cells. Based on the results of the REGARD (Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma) and the RAINBOW (Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastrooesophageal junction adenocarcinoma) studies ramucirumab was approved for 2nd line treatment as monotherapy and in combination with paclitaxel for patients with local relapse and unresectable or metastatic gastric cancer (including gastro-esophegal junction adenocarcinoma). Based on the results, in advanced solid malignancies, ramucirumab may prolong progression free survival and overall survival, although it may increase the risk of all adverse events (fatigue, neutropenia, haemorrhage, nausea, stomatitis). The authors review the clinical studies of ramucirumab. Rövidítések 5FU = 5-fluorouracil; AUC = görbe alatti terület; C min = minimális plazmakoncentráció; CI = konfidenciaintervallum; ECOG = Eastern Cooperative Oncology Group; FGFR = fibroblast növekedési faktor receptor; FOLFIRI = irinothecan, folinsav, 5-fluorouracil; FOLFOX = oxaliplatin, folinsav, 5-fluorouracil; GEJ = gastro...

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Ramucirumab: A Novel Antiangiogenic Agent

Cited by 30 publications

References 20 publications

Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer

Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer

Spotlight on ramucirumab in the treatment of nonsmall cell lung cancer: design, development, and clinical activity

Ramucirumab – egy új gyógyszer az onkológiában

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