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https://www.readbyqxmd.com/read/28780387/evaluation-of-the-response-of-intracranial-xenografts-to-vegf-signaling-inhibition-using-multiparametric-mri
#1
Jessica K R Boult, Gary Box, Maria Vinci, Lara Perryman, Suzanne A Eccles, Chris Jones, Simon P Robinson
Vascular endothelial growth factor A (VEGF-A) is considered one of the most important factors in tumor angiogenesis, and consequently, a number of therapeutics have been developed to inhibit VEGF signaling. Therapeutic strategies to target brain malignancies, both primary brain tumors, particularly in pediatric patients, and metastases, are lacking, but targeting angiogenesis may be a promising approach. Multiparametric MRI was used to investigate the response of orthotopic SF188(luc) pediatric glioblastoma xenografts to small molecule pan-VEGFR inhibitor cediranib and the effects of both cediranib and cross-reactive human/mouse anti-VEGF-A antibody B20-4...
August 3, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28655794/diffusion-mri-phenotypes-predict-overall-survival-benefitfrom-anti-vegf-monotherapy-in-recurrent-glioblastoma-converging-evidence-from-phase-ii-trials
#2
Benjamin M Ellingson, Elizabeth Gerstner, Marion Smits, Raymond Y Huang, Rivka R Colen, Lauren E Abrey, Dana T Aftab, Gisela M Schwab, Colin Hessel, Robert J Harris, Ararat Chakhoyan, Renske Gahrmann, Whitney B Pope, Kevin Leu, Catalina Raymond, Davis C Woodworth, John F de Groot, Patrick Y Wen, Tracy Batchelor, Martin J van den Bent, Timothy F Cloughesy
Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine. <br /><br />Experimental Design: Patients with recurrent GBM and diffusion MRI from the monotherapy arms of 5 separate Phase II clinical trials were included: 1) cediranib (NCT00035656); 2) bevacizumab (BRAIN Trial, AVF3708g; NCT00345163); 3) cabozantinib (XL184-201; NCT00704288); 4) aflibercept (VEGF Trap; NCT00369590); and 5) bevacizumab or lomustine (BELOB; NTR1929)...
June 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28599887/phase-i-trial-of-cediranib-in-combination-with-cisplatin-and-pemetrexed-in-chemonaive-patients-with-unresectable-malignant-pleural-mesothelioma-swog-s0905
#3
Anne S Tsao, James Moon, Ignacio I Wistuba, Nicholas J Vogelzang, Gregory P Kalemkerian, Mary W Redman, David R Gandara, Karen Kelly
INTRODUCTION: In malignant pleural mesothelioma, targeting angiogenesis with cediranib, a vascular endothelial growth factor receptor and platelet-derived growth factor receptor inhibitor, may have therapeutic potential. METHODS: S0905 phase I combined cediranib (two dose cohorts [30 mg and 20 mg daily]) with cisplatin-pemetrexed for six cycles followed by maintenance cediranib in unresectable chemonaive patients with malignant pleural mesothelioma of any histologic subtype...
August 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28559461/the-hgf-c-met-pathway-is-a-driver-and-biomarker-of-vegfr-inhibitor-resistance-and-vascular-remodeling-in-non-small-cell-lung-cancer
#4
Tina Cascone, Li Xu, Heather Y Lin, Wenbin Liu, Hai T Tran, Yuan Liu, Kathryn J Howells, Vincent Haddad, Emer O Hanrahan, Monique Nilsson, Maria Angelica Cortez, Uma Giri, Humam Kadara, Babita Saigal, Yun-Yong Park, Weiyi Peng, Ju-Seog Lee, Anderson J Ryan, Juliane M Juergensmeier, Roy S Herbst, Jing Wang, Robert R Langley, Ignacio I Wistuba, J Jack Lee, John Heymach
Resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the cellular mechanisms mediating resistance of NSCLCs to VEGFR tyrosine kinase inhibitors.<br /><br />Experimental Design: We generated murine models of human NSCLC and performed targeted inhibition studies with the VEGFR TKIs cediranib and vandetanib. We used species-specific hybridization of microarrays to compare cancer (human) and stromal (mouse) cell transcriptomes of TKI-sensitive and -resistant tumors...
May 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28477178/antiangiogenics-and-immunotherapies-in-cervical-cancer-an-update-and-future-s-view
#5
REVIEW
Daniela Luvero, Francesco Plotti, Salvatore Lopez, Giuseppe Scaletta, Stella Capriglione, Roberto Montera, Gianina Antonelli, Sara Ciuffreda, Raffaella Carassiti, Alice Oliveti, Roberto Angioli
Despite availability of primary and secondary prevention measures, cervical cancer (CC) persists as one of the most common cancers among women around the world, and more than 70% of cases are diagnosed at advanced stages. Although significant progress has been made in the treatment of CC, around 15-61% of patients develop a recurrence in lymph nodes or distant sites within the first 2 years of completing treatment and the prognosis for these patients remains poor. During the last decades, in an attempt to improve the outcome in these patients, novel agents as combination therapy that target known dysfunctional molecular pathways have been developed with the most attention to the inhibitors of the angiogenesis process...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28471727/safety-and-clinical-activity-of-the-programmed-death-ligand-1-inhibitor-durvalumab-in-combination-with-poly-adp-ribose-polymerase-inhibitor-olaparib-or-vascular-endothelial-growth-factor-receptor-1-3-inhibitor-cediranib-in-women-s-cancers-a-dose-escalation
#6
Jung-Min Lee, Ashley Cimino-Mathews, Cody J Peer, Alexandra Zimmer, Stanley Lipkowitz, Christina M Annunziata, Liang Cao, Maria I Harrell, Elizabeth M Swisher, Nicole Houston, Dana-Adriana Botesteanu, Janis M Taube, Elizabeth Thompson, Aleksandra Ogurtsova, Haiying Xu, Jeffers Nguyen, Tony W Ho, William D Figg, Elise C Kohn
Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition and/or reduced vascular endothelial growth factor signaling by vascular endothelial growth factor receptor inhibition may complement antitumor activity of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. Patients and Methods This phase I study tested durvalumab doublets in parallel 3 + 3 dose escalations...
July 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28454442/identification-of-target-genes-of-cediranib-in-alveolar-soft-part-sarcoma-using-a-gene-microarray
#7
Wenhua Jiang, Pengfei Liu, Xiaodong Li, Ping Wang
The aim of the present study was to identify the target genes of cediranib and the associated signaling pathways in alveolar soft part sarcoma (ASPS). A microarray dataset (GSE32569) was obtained from the Gene Expression Omnibus database. The R software package was used for data normalization and screening of differentially expressed genes (DEGs). The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology analysis. Gene Set Enrichment Analysis was performed to obtain the up- and downregulated pathways in ASPS...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28446504/feasibility-of-ultra-high-throughput-functional-screening-of-melanoma-biopsies-for-discovery-of-novel-cancer-drug-combinations
#8
Adam A Friedman, Yun Xia, Lorenzo Trippa, Long Phi Le, Vivien Igras, Dennie T Frederick, Jennifer A Wargo, Kenneth K Tanabe, Donald P Lawrence, Donna S Neuberg, Keith T Flaherty, David E Fisher
Purpose: Successful development of targeted therapy combinations for cancer patients depends on first discovering such combinations in predictive preclinical models. Stable cell lines and mouse xenograft models can have genetic and phenotypic drift and may take too long to generate to be useful as a personalized medicine tool.Experimental Design: To overcome these limitations, we have used a platform of ultra-high-throughput functional screening of primary biopsies preserving both cancer and stroma cell populations from melanoma patients to nominate such novel combinations from a library of thousands of drug combinations in a patient-specific manner within days of biopsy...
August 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28392095/real-time-analysis-of-the-binding-of-fluorescent-vegf165a-to-vegfr2-in-living-cells-effect-of-receptor-tyrosine-kinase-inhibitors-and-fate-of-internalized-agonist-receptor-complexes
#9
Laura E Kilpatrick, Rachel Friedman-Ohana, Diana C Alcobia, Kristin Riching, Chloe J Peach, Amanda J Wheal, Stephen J Briddon, Matthew B Robers, Kris Zimmerman, Thomas Machleidt, Keith V Wood, Jeanette Woolard, Stephen J Hill
Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. Here we have used a novel stoichiometric protein-labeling method to generate a fluorescent variant of VEGF (VEGF165a-TMR) labeled on a single cysteine within each protomer of the antiparallel VEGF homodimer. VEGF165a-TMR has then been used in conjunction with full length VEGFR2, tagged with the bioluminescent protein NanoLuc, to undertake a real time quantitative evaluation of VEGFR2 binding characteristics in living cells using bioluminescence resonance energy transfer (BRET)...
July 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28382802/major-clinical-research-advances-in-gynecologic-cancer-in-2016-10-year-special-edition
#10
REVIEW
Dong Hoon Suh, Miseon Kim, Kidong Kim, Hak Jae Kim, Kyung Hun Lee, Jae Weon Kim
In 2016, 13 topics were selected as major research advances in gynecologic oncology. For ovarian cancer, study results supporting previous ones regarding surgical preventive strategies were reported. There were several targeted agents that showed comparable responses in phase III trials, including niraparib, cediranib, and nintedanib. On the contrary to our expectations, dose-dense weekly chemotherapy regimen failed to prove superior survival outcomes compared with conventional triweekly regimen. Single-agent non-platinum treatment to prolong platinum-free-interval in patients with recurrent, partially platinum-sensitive ovarian cancer did not improve and even worsened overall survival (OS)...
May 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28360207/-18-f-fluoromisonidazole-kinetic-modeling-for-characterization-of-tumor-perfusion-and-hypoxia-in-response-to-antiangiogenic-therapy
#11
Milan Grkovski, Sally-Ann Emmas, Sean D Carlin
Multiparametric imaging of tumor perfusion and hypoxia with (18)F-fluoromisonidazole ((18)F-FMISO) dynamic positron emission tomography (dPET) may allow for an improved response assessment to antiangiogenic therapies. Cediranib (AZD2171) is a potent inhibitor of tyrosine kinase activity associated with vascular endothelial growth factor receptors-1, -2 and -3, currently in Phase II/III clinical trials. Serial (18)F-FMISO dPET was performed to investigate changes in tumor biomarkers of perfusion and hypoxia following cediranib treatment...
March 30, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28339098/quality-of-life-with-cediranib-in-relapsed-ovarian-cancer-the-icon6-phase-3-randomized-clinical-trial
#12
Dan P Stark, Adrian Cook, Julia M Brown, Michael D Brundage, Andrew C Embleton, Richard S Kaplan, Fharat A Raja, Ann Marie W Swart, Galina Velikova, Wendi Qian, Jonathan A Ledermann
BACKGROUND: The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment. METHODS: Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance...
July 15, 2017: Cancer
https://www.readbyqxmd.com/read/28259301/effectiveness-of-antiangiogenic-drugs-in-glioblastoma-patients-a-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#13
REVIEW
Giuseppe Lombardi, Ardi Pambuku, Luisa Bellu, Miriam Farina, Alessandro Della Puppa, Luca Denaro, Vittorina Zagonel
BACKGROUND: glioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results. We performed a systematic review and a meta-analysis to clarify and evaluate their effectiveness in glioblastoma patients. PATIENTS AND METHODS: we searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from January 2006 to January 2016 in MEDLINE, WEB of SCIENCE, ASCO, ESMO and SNO databases...
March 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28213941/population-pharmacokinetic-and-exposure-simulation-analysis-for-cediranib-azd2171-in-pooled-phase-i-ii-studies-in-patients-with-cancer
#14
Jianguo Li, Nidal Al-Huniti, Anja Henningsson, Weifeng Tang, Eric Masson
AIMS: A population pharmacokinetic (PK) model was developed for cediranib to simulate cediranib exposure for different doses, including comedication with strong uridine glucuronosyl transferase/P-glycoprotein inducers such as rifampicin, in cancer patients. METHODS: Plasma concentrations and covariates from 625 cancer patients after single or multiple oral cediranib administrations ranging from 0.5 to 90 mg in 19 Phase I and II studies were included in the analysis...
August 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28138259/advances-in-antiangiogenic-treatment-of-small-cell-lung-cancer
#15
REVIEW
Hongyang Lu, Zhiming Jiang
Small-cell lung cancer (SCLC), a poorly differentiated neuroendocrine malignancy, has a rapid growth rate, strong aggressiveness, early metastases, and poor prognosis. Angiogenesis greatly contributes to the metastatic process of SCLC, which has a higher vascularization compared with non-small-cell lung cancer (NSCLC). SCLC might constitute an ideal malignancy for assessing new antiangiogenic drugs and therapeutic strategies. Combining bevacizumab with paclitaxel has therapeutic benefits in chemoresistant, relapsed SCLC...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28002822/the-vegfr-inhibitor-cediranib-improves-the-efficacy-of-fractionated-radiotherapy-in-a-colorectal-cancer-xenograft-model
#16
Elodie Melsens, Bert Verberckmoes, Natacha Rosseel, Christian Vanhove, Benedicte Descamps, Piet Pattyn, Wim Ceelen
BACKGROUND/PURPOSE: Radiotherapy (RT) increases local tumor control in locally advanced rectal cancer, but complete histological response is seen in only a minority of cases. Antiangiogenic therapy has been proposed to improve RT efficacy by "normalizing" the tumor microvasculature. Here, we examined whether cediranib, a pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, improves microvascular function and tumor control in combination with RT in a mouse colorectal cancer (CRC) model...
2017: European Surgical Research. Europäische Chirurgische Forschung. Recherches Chirurgicales Européennes
https://www.readbyqxmd.com/read/27986807/effects-of-4-multitargeted-receptor-tyrosine-kinase-inhibitors-on-regional-hemodynamics-in-conscious-freely-moving-rats
#17
Joanne J Carter, Laurice V Fretwell, Jeanette Woolard
VEGF inhibitors, including receptor tyrosine kinase inhibitors, are used as adjunct therapies in a number of cancer treatments. An emerging issue with these drugs is that most cause hypertension. To gain insight into the physiological mechanisms involved, we evaluated their regional hemodynamic effects in conscious rats. Male Sprague Dawley rats (350-450 g) were chronically implanted with pulsed Doppler flow probes (renal and mesenteric arteries, and the descending abdominal aorta) and catheters (jugular vein, peritoneal cavity, and distal abdominal aorta)...
March 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27943222/clinical-pharmacokinetics-and-pharmacodynamics-of-cediranib
#18
REVIEW
Weifeng Tang, Alex McCormick, Jianguo Li, Eric Masson
Cediranib potently and selectively inhibits all three vascular endothelial growth factor receptors (VEGFR-1, -2 and -3), and clinical studies have shown that it is effective in patients with ovarian cancer at a dose of 20 mg/day. Cediranib is absorbed moderately slowly; a high-fat meal reduced the cediranib area under the plasma concentration-time curve (AUC) by 24% and maximum plasma concentration (C max) by 33%. Cediranib binds to serum albumin and α1-acid glycoprotein; protein binding in human plasma is approximately 95%...
December 9, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27940520/exploring-the-benefit-risk-associated-with-antiangiogenic-agents-for-the-treatment-of-non-small-cell-lung-cancer-patients
#19
REVIEW
Razelle Kurzrock, David J Stewart
Following the approval of bevacizumab, an antibody targeting VEGF-A, for advanced non-squamous non-small cell lung cancer (NSCLC) in 2006, intensive efforts were put into the clinical development of antiangiogenic agents for NSCLC. Currently, the other antiangiogenic agents approved for NSCLC are ramucirumab, a VEGF receptor-2 (VEGFR-2)-targeting antibody indicated for both squamous and non-squamous NSCLC in the United States, and nintedanib, an anti-VEGFR-1/2/3, platelet-derived growth factor receptor-α/β, fibroblast growth factor receptor-1/2/3 angiokinase inhibitor indicated for adenocarcinoma of the lung in the European Union...
March 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27920695/metastatic-alveolar-soft-part-sarcoma-responsive-to-pazopanib-after-progression-through-sunitinib-and-bevacizumab-two-cases
#20
William L Read, Felicia Williams
Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with a propensity for lung metastases and indolent progression. ASPS is not responsive to chemotherapy, but there are case reports and small series describing benefit from drugs targeting the VEGF pathway. These drugs include sunitinib, cediranib and bevacizumab. There is no established second-line treatment for persons with ASPS progressing through first-line targeted therapy. We report two individuals with metastatic ASPS who obtained disease stabilization from sunitinib lasting over a year...
September 2016: Case Reports in Oncology
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