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Cediranib

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https://www.readbyqxmd.com/read/27781258/-research-status-quo-and-progression-in-targeted-therapy-for-advanced-gastric-cancer
#1
Rui Feng, Xiaotian Zhang, Sheng Yang
With the deeper research of the proliferation, invasion and metastasis mechanisms of the gastric cancer, targeted therapy has become a hot spot in this field. The exploration of targeted agents for gastric cancer is mainly concentrated upon the drugs that target human epidermal growth factor receptor (HER) family, the vascular endothelial growth factor (VEGF), the phosphatidylinositol 3-kinase-protein kinase/mammalian target of rapamycin (PI3K/mTOR) and the NF-κB signaling pathways. The targeted drugs relevant to HER family include the Cetuximab, Nimotuzumab, Matuzumab, Panitumumab and Erlotinib which are aimed at HER-1, the Trastuzumab, Pertuzumab and T-DM1 (trastuzumab emtansine) which are aimed at HER-2, and the Lapatinib and Afatinib which are the multi-target agents of HER...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27748845/microrna-profiling-in-human-breast-cancer-cell-lines-exposed-to-the-anti-neoplastic-drug-cediranib
#2
A L R Bordinhão, A F Evangelista, R J S Oliveira, T Macedo, H C Silveira, R M Reis, M M Marques
Cediranib, a pan-tyrosine kinase inhibitor is showing promising results for the treatment of several solid tumours. In breast cancer, its effects remain unclear, and there are no predictive biomarkers. Several studies have examined the expression profiles of microRNAs (miRNAs) in response to different chemotherapy treatments and found that the expression patterns may be associated with the treatment response. Therefore, our aim was to evaluate the cellular behaviour and differential expression profiles of miRNAs in breast cancer cell lines exposed to cediranib...
October 7, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27486869/the-emerging-role-of-tyrosine-kinase-inhibitors-in-ovarian-cancer-treatment-a-systematic-review
#3
Ioannis Ntanasis-Stathopoulos, George Fotopoulos, Ioannis-Georgios Tzanninis, Elias A Kotteas
The present systematic review summarizes current evidence regarding the mechanisms of action, the efficacy, and the adverse effects of tyrosine kinase inhibitors (TKIs) in ovarian cancer patients. Phase II and III clinical trials were sought in the PubMed database and in the Clinical Trials.gov registry through September 30, 2015. Seventy-five clinical trials regarding TKIs targeting mainly vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, and sarcoma tyrosine kinase (Src) were yielded...
August 8, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27232884/multi-center-randomized-phase-ii-study-comparing-cediranib-plus-gefitinib-with-cediranib-plus-placebo-in-subjects-with-recurrent-progressive-glioblastoma
#4
Nicholas Brown, Catherine McBain, Stephen Nash, Kirsten Hopkins, Paul Sanghera, Frank Saran, Mark Phillips, Fiona Dungey, Laura Clifton-Hadley, Katharina Wanek, Daniel Krell, Sarah Jeffries, Iftekhar Khan, Paul Smith, Paul Mulholland
BACKGROUND: Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. METHODS AND FINDINGS: This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy...
2016: PloS One
https://www.readbyqxmd.com/read/27052640/pharmacotherapies-for-the-treatment-of-glioblastoma-current-evidence-and-perspectives
#5
Katharina Seystahl, Dorothee Gramatzki, Patrick Roth, Michael Weller
INTRODUCTION: Glioblastoma, the most common malignant brain tumor, exhibits a poor prognosis with little therapeutic progress in the last decade. Novel treatment strategies beyond the established standard of care with temozolomide-based radiotherapy are urgently needed. AREAS COVERED: We reviewed the literature on glioblastoma with a focus on phase III trials for pharmacotherapies and/or innovative concepts until December 2015. EXPERT OPINION: In the last decade, phase III trials on novel compounds largely failed to introduce efficacious pharmacotherapies beyond temozolomide in glioblastoma...
June 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27044097/dual-inhibition-of-ang-2-and-vegf-receptors-normalizes-tumor-vasculature-and-prolongs-survival-in-glioblastoma-by-altering-macrophages
#6
Teresa E Peterson, Nathaniel D Kirkpatrick, Yuhui Huang, Christian T Farrar, Koen A Marijt, Jonas Kloepper, Meenal Datta, Zohreh Amoozgar, Giorgio Seano, Keehoon Jung, Walid S Kamoun, Trupti Vardam, Matija Snuderl, Jermaine Goveia, Sampurna Chatterjee, Ana Batista, Alona Muzikansky, Ching Ching Leow, Lei Xu, Tracy T Batchelor, Dan G Duda, Dai Fukumura, Rakesh K Jain
Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits of anti-VEGF receptor (VEGFR) treatment in murine GBM models and that circulating Ang-2 levels in GBM patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition of VEGFR/Ang-2 could improve survival in two orthotopic models of GBM, Gl261 and U87...
April 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27025186/cediranib-in-patients-with-relapsed-platinum-sensitive-ovarian-cancer-icon6-a-randomised-double-blind-placebo-controlled-phase-3-trial
#7
RANDOMIZED CONTROLLED TRIAL
Jonathan A Ledermann, Andrew C Embleton, Fharat Raja, Timothy J Perren, Gordon C Jayson, Gordon J S Rustin, Stan B Kaye, Hal Hirte, Elizabeth Eisenhauer, Michelle Vaughan, Michael Friedlander, Antonio González-Martín, Daniel Stark, Elizabeth Clark, Laura Farrelly, Ann Marie Swart, Adrian Cook, Richard S Kaplan, Mahesh K B Parmar
BACKGROUND: Angiogenesis is a validated clinical target in advanced epithelial ovarian cancer. Cediranib is an oral antiangiogenic vascular endothelial growth factor receptor 1-3 inhibitor that has shown antitumour activity in recurrent ovarian cancer. We assessed efficacy and safety of cediranib in combination with platinum-based chemotherapy and as continued maintenance treatment in patients with first relapse of platinum-sensitive ovarian cancer. METHODS: In this randomised, three-arm, double-blind, placebo-controlled phase 3 trial, we randomly assigned patients aged 18 years or older with relapsed platinum-sensitive ovarian cancer at 63 centres in Australia, Canada, New Zealand, Spain, and the UK...
March 12, 2016: Lancet
https://www.readbyqxmd.com/read/27009237/autocrine-vegfr1-and-vegfr2-signaling-promotes-survival-in-human-glioblastoma-models-in-vitro-and-in-vivo
#8
Emese Szabo, Hannah Schneider, Katharina Seystahl, Elisabeth Jane Rushing, Frank Herting, K Michael Weidner, Michael Weller
BACKGROUND: Although the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system has become a prime target for antiangiogenic treatment, its biological role in glioblastoma beyond angiogenesis has remained controversial. METHODS: Using neutralizing antibodies to VEGF or placental growth factor (PlGF) or the tyrosine kinase inhibitor, cediranib, or lentiviral gene silencing, we delineated autocrine signaling in glioma cell lines. The in vivo effects of VEGFR1 and VEGFR2 depletion were evaluated in orthotopic glioma xenograft models...
September 2016: Neuro-oncology
https://www.readbyqxmd.com/read/26931561/histology-specific-uses-of-tyrosine-kinase-inhibitors-in-non-gastrointestinal-stromal-tumor-sarcomas
#9
Tarsheen K Sethi, Vicki L Keedy
Adult sarcomas, especially those with metastatic or unresectable disease, have limited treatment options. Traditional chemotherapeutic options have been limited by poor response rates in patients with advanced sarcomas. The important clinical question is whether the success of targeted therapy in GIST can be extended to other sarcomas and also if preclinical data describing targets across this heterogeneous group of cancers can be translated to clinical efficacy of known and upcoming target specific agents...
February 2016: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/26929887/long-term-remission-over-six-years-for-a-patient-with-recurrent-glioblastoma-treated-with-cediranib-lomustine
#10
Doniel Drazin, Lutfi Al-Khouja, Ashish Patel, Jethro Hu, Surasak Phuphanich
Cediranib is an orally available, pan-VEGFR tyrosine kinase inhibitor. A previous Phase III study of patients with recurrent glioblastoma treated with this drug did not meet the primary end of progressive-free survival (PFS). We identified one patient, a 57-year-old Caucasian female who, following surgery in October 2008 and concurrent temozolomide and radiation therapy from November 8, 2008, to January 6, 2009, developed a tumor progression of the left posterior frontal measuring 1.2 x 1.5 cm in February 2009...
2016: Curēus
https://www.readbyqxmd.com/read/26899229/cediranib-a-pan-vegfr-inhibitor-and-olaparib-a-parp-inhibitor-in-combination-therapy-for-high-grade-serous-ovarian-cancer
#11
S Percy Ivy, Joyce F Liu, Jung-Min Lee, Ursula A Matulonis, Elise C Kohn
INTRODUCTION: An estimated 22,000 women are diagnosed annually with ovarian cancer in the United States. Initially chemo-sensitive, recurrent disease ultimately becomes chemoresistant and may kill ~14,000 women annually. Molecularly targeted therapy with cediranib (AZD2171), a vascular endothelial growth factor receptor (VEGFR)-1, 2, and 3 signaling blocker, and olaparib (AZD2281), a poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor, administered orally in combination has shown anti-tumor activity in the treatment of high grade serous ovarian cancer (HGSOC)...
2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/26841902/a-phase-ii-study-of-cediranib-an-oral-vegf-inhibitor-in-previously-untreated-patients-with-metastatic-or-recurrent-malignant-melanoma
#12
Elaine McWhirter, Ian Quirt, Thomas Gajewski, Gregory Pond, Lisa Wang, June Hui, Amit Oza
PURPOSE: A two stage multi-institution Phase II study was undertaken by the Princess Margaret Hospital Consortium to evaluate the efficacy and toxicity of oral cediranib, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with previously untreated advanced malignant melanoma. PATIENTS AND METHODS: Between May 2006 and April 2008, 24 patients (median age 65 years) with advanced malignant melanoma were treated with oral cediranib. Cediranib was given on a continuous, oral once daily schedule of 45 mg, on a 28 day cycle...
April 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/26802156/a-randomized-double-blind-phase-ii-study-evaluating-cediranib-versus-cediranib-and-saracatinib-in-patients-with-relapsed-metastatic-clear-cell-renal-cancer-cosak
#13
T Powles, J Brown, J Larkin, R Jones, C Ralph, R Hawkins, S Chowdhury, E Boleti, A Bhal, K Fife, A Webb, S Crabb, T Geldart, R Hill, J Dunlop, P E Hall, D McLaren, C Ackerman, L Beltran, P Nathan
BACKGROUND: Preclinical work suggests SRC proteins have a role in the development of resistance to vascular endothelial growth factor (VEGF) targeted therapy in metastatic clear-cell renal cancer (mRCC). This hypothesis was tested in this trial using the SRC inhibitor saracatinib and the VEGF inhibitor cediranib. PATIENTS AND METHODS: Patients with disease progression after ≥1 VEGF-targeted therapy were eligible to participate in this double-blind, randomized (1:1) phase II study...
May 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/26645582/pleiotrophin-promotes-vascular-abnormalization-in-gliomas-and-correlates-with-poor-survival-in-patients-with-astrocytomas
#14
Lei Zhang, Soumi Kundu, Tjerk Feenstra, Xiujuan Li, Chuan Jin, Liisi Laaniste, Tamador Elsir Abu El Hassan, K Elisabet Ohlin, Di Yu, Tommie Olofsson, Anna-Karin Olsson, Fredrik Pontén, Peetra U Magnusson, Karin Forsberg Nilsson, Magnus Essand, Anja Smits, Lothar C Dieterich, Anna Dimberg
Glioblastomas are aggressive astrocytomas characterized by endothelial cell proliferation and abnormal vasculature, which can cause brain edema and increase patient morbidity. We identified the heparin-binding cytokine pleiotrophin as a driver of vascular abnormalization in glioma. Pleiotrophin abundance was greater in high-grade human astrocytomas and correlated with poor survival. Anaplastic lymphoma kinase (ALK), which is a receptor that is activated by pleiotrophin, was present in mural cells associated with abnormal vessels...
December 8, 2015: Science Signaling
https://www.readbyqxmd.com/read/26645398/synergistic-antivascular-and-antitumor-efficacy-with-combined-cediranib-and-sc6889-in-intracranial-mouse-glioma
#15
Merryl R Lobo, Ayaka Kukino, Huong Tran, Matthias C Schabel, Charles S Springer, G Yancey Gillespie, Marjorie R Grafe, Randall L Woltjer, Martin M Pike
Prognosis remains extremely poor for malignant glioma. Targeted therapeutic approaches, including single agent anti-angiogenic and proteasome inhibition strategies, have not resulted in sustained anti-glioma clinical efficacy. We tested the anti-glioma efficacy of the anti-angiogenic receptor tyrosine kinase inhibitor cediranib and the novel proteasome inhibitor SC68896, in combination and as single agents. To assess anti-angiogenic effects and evaluate efficacy we employed 4C8 intracranial mouse glioma and a dual-bolus perfusion MRI approach to measure Ktrans, relative cerebral blood flow and volume (rCBF, rCBV), and relative mean transit time (rMTT) in combination with anatomical MRI measurements of tumor growth...
2015: PloS One
https://www.readbyqxmd.com/read/26626460/leptin-bmi-and-a-metabolic-gene-expression-signature-associated-with-clinical-outcome-to-vegf-inhibition-in-colorectal-cancer
#16
Aurélien J C Pommier, Matthew Farren, Bhavika Patel, Mark Wappett, Filippos Michopoulos, Neil R Smith, Jane Kendrew, Jeremy Frith, Russell Huby, Catherine Eberlein, Hayley Campbell, Christopher Womack, Paul D Smith, Jane Robertson, Shethah Morgan, Susan E Critchlow, Simon T Barry
VEGF (vascular endothelial growth factor) signaling inhibitors are widely used in different cancer types; however, patient selection remains a challenge. Analyses of samples from a phase III clinical trial in metastatic colorectal cancer testing chemotherapy versus chemotherapy with the small molecule VEGF receptors inhibitor cediranib identified circulating leptin levels, BMI, and a tumor metabolic and angiogenic gene expression signature associated with improved clinical outcome in patients treated with cediranib...
January 12, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/26474520/clinical-implications-for-cediranib-in-advanced-cervical-cancer
#17
COMMENT
Krishnansu S Tewari
No abstract text is available yet for this article.
November 2015: Lancet Oncology
https://www.readbyqxmd.com/read/26474517/cediranib-combined-with-carboplatin-and-paclitaxel-in-patients-with-metastatic-or-recurrent-cervical-cancer-circca-a-randomised-double-blind-placebo-controlled-phase-2-trial
#18
RANDOMIZED CONTROLLED TRIAL
R Paul Symonds, Charlie Gourley, Susan Davidson, Karen Carty, Elaine McCartney, Debbie Rai, Susana Banerjee, David Jackson, Rosemary Lord, Mary McCormack, Emma Hudson, Nicholas Reed, Maxine Flubacher, Petra Jankowska, Melanie Powell, Caroline Dive, Catharine M L West, James Paul
BACKGROUND: Patients treated with standard chemotherapy for metastatic or relapsed cervical cancer respond poorly to conventional chemotherapy (response achieved in 20-30% of patients) with an overall survival of less than 1 year. High tumour angiogenesis and high concentrations of intratumoural VEGF are adverse prognostic features. Cediranib is a potent tyrosine kinase inhibitor of VEGFR1, 2, and 3. In this trial, we aimed to assess the effect of the addition of cediranib to carboplatin and paclitaxel chemotherapy in patients with metastatic or recurrent cervical cancer...
November 2015: Lancet Oncology
https://www.readbyqxmd.com/read/26461489/landscape-of-targeted-anti-cancer-drug-synergies-in-melanoma-identifies-a-novel-braf-vegfr-pdgfr-combination-treatment
#19
Adam A Friedman, Arnaud Amzallag, Iulian Pruteanu-Malinici, Subash Baniya, Zachary A Cooper, Adriano Piris, Leeza Hargreaves, Vivien Igras, Dennie T Frederick, Donald P Lawrence, Daniel A Haber, Keith T Flaherty, Jennifer A Wargo, Sridhar Ramaswamy, Cyril H Benes, David E Fisher
A newer generation of anti-cancer drugs targeting underlying somatic genetic driver events have resulted in high single-agent or single-pathway response rates in selected patients, but few patients achieve complete responses and a sizeable fraction of patients relapse within a year. Thus, there is a pressing need for identification of combinations of targeted agents which induce more complete responses and prevent disease progression. We describe the results of a combination screen of an unprecedented scale in mammalian cells performed using a collection of targeted, clinically tractable agents across a large panel of melanoma cell lines...
2015: PloS One
https://www.readbyqxmd.com/read/26459812/current-status-and-future-directions-of-anti-angiogenic-therapy-for-gliomas
#20
REVIEW
Wolfgang Wick, Michael Platten, Antje Wick, Anne Hertenstein, Alexander Radbruch, Martin Bendszus, Frank Winkler
Molecular targets for the pathological vasculature are the vascular endothelial growth factor (VEGF)/VEGF receptor axis, integrins, angiopoietins, and platelet-derived growth factor receptor (PDGFR), as well as several intracellular or downstream effectors like protein kinase C beta and mammalian target of rapamycin (mTOR). Besides hypoxic damage or tumor cell starvation, preclinical models imply vessel independent tumor regression and suggest differential effects of anti-angiogenic treatments on tumorous and nontumorous precursor cells or the immune system...
March 2016: Neuro-oncology
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