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Predictive biomarkers bevacizumab

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https://www.readbyqxmd.com/read/28499022/quantitative-imaging-biomarkers-for-risk-stratification-of-patients-with-recurrent-glioblastoma-treated-with-bevacizumab
#1
Patrick Grossmann, Vivek Narayan, Ken Chang, Rifaquat Rahman, Lauren Abrey, David A Reardon, Lawrence H Schwartz, Patrick Y Wen, Brian M Alexander, Raymond Huang, Hugo J W L Aerts
Background: Antiangiogenic therapy with bevacizumab is the most widely used treatment option for recurrent glioblastoma, but therapeutic response varies substantially and effective biomarkers for patient selection are not available. To this end, we determine whether novel quantitative radiomic strategies on the basis of magnetic-resonance-imaging (MRI) have the potential to noninvasively stratify survival and progression in this patient population. Methods: In an initial cohort of 126 patients, we identified a distinct set of features representative of the radiographic phenotype on baseline (pre-treatment) MRI...
May 11, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28487489/apelin-a-putative-novel-predictive-biomarker-for-bevacizumab-response-in-colorectal-cancer
#2
Linda Zuurbier, Arman Rahman, Martijn Cordes, Jennifer Scheick, Tse J Wong, François Rustenburg, Jesu Christopher Joseph, Peter Dynoodt, Rory Casey, Paul Drillenburg, Michael Gerhards, Ana Barat, Rut Klinger, Bozena Fender, Darran P O'Connor, Johannes Betge, Matthias P Ebert, Timo Gaiser, Jochen H M Prehn, Arjan W Griffioen, Nicole C T van Grieken, Bauke Ylstra, Annette T Byrne, Laurens G van der Flier, William M Gallagher, Ruben Postel
Bevacizumab (bvz) is currently employed as an anti-angiogenic therapy across several cancer indications. Bvz response heterogeneity has been well documented, with only 10-15% of colorectal cancer (CRC) patients benefitting in general. For other patients, clinical efficacy is limited and side effects are significant. This reinforces the need for a robust predictive biomarker of response. To identify such a biomarker, we performed a DNA microarray-based transcriptional profiling screen with primary endothelial cells (ECs) isolated from normal and tumour colon tissues...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28465540/circulating-vegf-and-enos-variations-as-predictors-of-outcome-in-metastatic-colorectal-cancer-patients-receiving-bevacizumab
#3
Giorgia Marisi, Emanuela Scarpi, Alessandro Passardi, Oriana Nanni, Angela Ragazzini, Martina Valgiusti, Andrea Casadei Gardini, Luca Maria Neri, Giovanni Luca Frassineti, Dino Amadori, Paola Ulivi
Novel predictive biomarkers are needed to improve patient selection and optimize the use of bevacizumab (B) in metastatic colorectal cancer. We analyzed the potential of five circulating biomarkers to predict B efficacy and monitor response. Peripheral blood samples collected at baseline, at the first clinical evaluation and at progression were available for 129 patients enrolled in the prospective multicentric ITACa trial and randomized to receive FOLFOX4/FOLFIRI (CT) with (64 patients) or without B (65 patients)...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28451421/role-of-ras-mutation-status-as-a-prognostic-factor-for-patients-with-advanced-colorectal-cancer-treated-with-first-line-chemotherapy-based-on-fluoropyrimidines-and-oxaliplatin-with-or-without-bevavizumab-a-retrospective-analysis
#4
Javier Garde Noguera, Eloisa Jantus-Lewintre, Mireia Gil-Raga, Elena Evgenyeva, Sonia Maciá Escalante, Antonio Llombart-Cussac, Carlos Camps Herrero
The role of Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) mutations as negative predictors for anti-epidermal growth factor receptor (EGFR) therapies in metastatic colorectal cancer (CRC) has been firmly established. However, whether the RAS mutation status plays a role as a biomarker for anti-vascular endothelial growth factor (VEGF) treatment remains controversial. Data from 93 CRC patients who received first-line cytotoxic chemotherapy with fluoropyrimidines and oxaliplatin, with or without bevacizumab, were analyzed...
March 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28430038/prognostic-implications-of-the-subcellular-localization-of-survivin-in-glioblastomas-treated-with-radiotherapy-plus-concomitant-and-adjuvant-temozolomide
#5
Taiichi Saito, Kazuhiko Sugiyama, Yukio Takeshima, Vishwa Jeet Amatya, Fumiyuki Yamasaki, Takeshi Takayasu, Ryo Nosaka, Yoshihiro Muragaki, Takakazu Kawamata, Kaoru Kurisu
OBJECTIVE Currently, the standard treatment protocol for patients with newly diagnosed glioblastoma (GBM) includes surgery, radiotherapy, and concomitant and adjuvant temozolomide (TMZ). Various prognostic biomarkers for GBM have been described, including survivin expression. The aim of this study was to determine whether the subcellular localization of survivin correlates with GBM prognosis in patients who received the standard treatment protocol. METHODS The authors retrospectively examined the subcellular localization of survivin (nuclear, cytoplasmic, or both) using immunohistochemistry in 50 patients with GBM who had received the standard treatment...
April 21, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28386777/bevacizumab-for-malignant-gliomas-current-indications-mechanisms-of-action-and-resistance-and-markers-of-response
#6
Ryota Tamura, Toshihide Tanaka, Keisuke Miyake, Kazunari Yoshida, Hikaru Sasaki
Vascular endothelial growth factor (VEGF) is an attractive target of antiangiogenic therapy in glioblastomas. Bevacizumab (Bev), a humanized anti-VEGF antibody, is associated with the improvement of progression-free survival and performance status in patients with glioblastoma. However, randomized trials uniformly suggest that these favorable clinical effects of Bev do not translate into an overall survival benefit. The mechanisms of action of Bev appear to include the inhibition of tumor angiogenesis, as well as indirect effects such as the depletion of niches for glioma stem cells and stimulation of antitumor immunity...
April 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28376174/role-of-yap1-as-a-marker-of-sensitivity-to-dual-akt-and-p70s6k-inhibition-in-ovarian-and-uterine-malignancies
#7
Rebecca A Previs, Guillermo N Armaiz-Pena, Cristina Ivan, Heather J Dalton, Rajesha Rupaimoole, Jean M Hansen, Yasmin Lyons, Jie Huang, Monika Haemmerle, Michael J Wagner, Kshipra M Gharpure, Archana S Nagaraja, Justyna Filant, Michael H McGuire, Kyunghee Noh, Piotr L Dorniak, Sarah L Linesch, Lingegowda S Mangala, Sunila Pradeep, Sherry Y Wu, Anil K Sood
Background: The PI3K/AKT/P70S6K pathway is an attractive therapeutic target in ovarian and uterine malignancies because of its high rate of deregulation and key roles in tumor growth. Here, we examined the biological effects of MSC2363318A, which is a novel inhibitor of AKT1, AKT3, and P70S6K. Methods: Orthotopic murine models of ovarian and uterine cancer were utilized to study the effect of MSC2363318A on survival and regression. For each cell line, 10 mice were treated in each of the experimental arms tested...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28359318/24h-gene-variation-effect-of-combined-bevacizumab-erlotinib-in-advanced-non-squamous-non-small-cell-lung-cancer-using-exon-array-blood-profiling
#8
Florent Baty, Markus Joerger, Martin Früh, Dirk Klingbiel, Francesco Zappa, Martin Brutsche
BACKGROUND: The SAKK 19/05 trial investigated the safety and efficacy of the combined targeted therapy bevacizumab and erlotinib (BE) in unselected patients with advanced non-squamous non-small cell lung cancer (NSCLC). Although activating EGFR mutations were the strongest predictors of the response to BE, some patients not harboring driver mutations could benefit from the combined therapy. The identification of predictive biomarkers before or short after initiation of therapy is therefore paramount for proper patient selection, especially among EGFR wild-types...
March 30, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28347919/autophagy-related-polymorphisms-predict-hypertension-in-patients-with-metastatic-colorectal-cancer-treated-with-folfiri-and-bevacizumab-results-from-tribe-and-fire-3-trials
#9
Martin D Berger, Shinichi Yamauchi, Shu Cao, Diana L Hanna, Yu Sunakawa, Marta Schirripa, Satoshi Matsusaka, Dongyun Yang, Susan Groshen, Wu Zhang, Yan Ning, Satoshi Okazaki, Yuji Miyamoto, Mitsukuni Suenaga, Sara Lonardi, Chiara Cremolini, Alfredo Falcone, Volker Heinemann, Fotios Loupakis, Sebastian Stintzing, Heinz-Josef Lenz
PURPOSE: The most frequent bevacizumab-related side-effects are hypertension, proteinuria, bleeding and thromboembolism. To date, there is no biomarker that predicts anti-VEGF-associated toxicity. As autophagy inhibits angiogenesis, we hypothesised that single-nucleotide polymorphisms (SNPs) within autophagy-related genes may predict bevacizumab-mediated toxicity in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with mCRC treated with first-line FOLFIRI and bevacizumab in two phase III randomised trials, namely the TRIBE trial (n = 219, discovery cohort) and the FIRE-3 trial (n = 234, validation cohort) were included in this study...
March 24, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28303751/vasoactive-peptides-associate-with-treatment-outcome-ofbevacizumab-containing-therapy-in-metastatic-colorectal-cancer
#10
Helga Hagman, Pär-Ola Bendahl, Olle Melander, Jan Sundberg, Anders Johnsson, Mattias Belting
BACKGROUND: Hypertension is a common early adverse event of anti-angiogenic treatment of cancer and may associate with treatment response. However, blood pressure measurement as a surrogate response biomarker has methodological limitations, and predictive biomarkers of angiogenesis inhibitors are lacking. In disease associated with hypertension, vasoactive peptides have been linked to cardiovascular pressure load. Here, we have explored potential associations between circulating levels of vasoactive peptides and tumor response during bevacizumab-containing treatment of colorectal cancer...
March 17, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28298545/homeobox-b9-mediates-resistance-to-anti-vegf-therapy-in-colorectal-cancer-patients
#11
Carmine Carbone, Geny Piro, Francesca Simionato, Francesca Ligorio, Chiara Cremolini, Fotios Loupakis, Greta Alì, Daniele Rossini, Valeria Merz, Raffaela Santoro, Camilla Zecchetto, Marco Zanotto, Federica Di Nicolantonio, Alberto Bardelli, Gabriella Fontanini, Giampaolo Tortora, Davide Melisi
PURPOSE: The identification of predictive biomarkers for antiangiogenic therapies remains an unmeet need. We hypothesized that the transcription factor Homeobox B9 (HOXB9) could be responsible for the tumor resistance to the anti-VEGF agent bevacizumab. EXPERIMENTAL DESIGN: HOXB9 expression and activation were measured in eight models of colorectal and pancreatic cancer with different resistance to bevacizumab. Serum levels of Angiopoietin-like Protein (Angptl)2, CXC receptor ligand (CXCL)1, interleukin(IL)8, and Transforming Growth Factor (TGF)β1 in tumor-bearing mice were measured by multiplex xMAP technology...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28286925/cabozantinib-for-renal-cell-carcinoma-current-and-future-paradigms
#12
REVIEW
Ahmed Abdelaziz, Ulka Vaishampayan
Cabozantinib was approved by the FDA in April 2016 for the treatment of advanced renal cancer, pretreated with at least one prior antiangiogenic therapy. This is the first agent in the therapy of kidney cancer to show a statistically significant improvement in all three endpoints of clinical efficacy, response rate, progression free survival, and overall survival (OS), in a phase III randomized trial. The reporting of METEOR coincided with that of the Checkmate 025 study which randomized similarly eligible patients to receive nivolumab or everolimus 10 mg daily...
March 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28286565/everolimus-in-the-management-of-metastatic-neuroendocrine-tumours
#13
REVIEW
David L Chan, Eva Segelov, Simron Singh
Neuroendocrine tumours are increasing in incidence and cause a variety of symptoms. The mammalian target of rapamycin (mTOR) pathway plays a key role in neuroendocrine tumour (NET) pathogenesis, leading to increased lipid synthesis, protein synthesis and cellular growth. Upregulation of this pathway is noted in both hereditary and sporadic NETs. This understanding has led to investigations of mTOR inhibitors as therapy for metastatic NETs. After promising preclinical findings, everolimus, an mTOR inhibitor, was trialled in the RADIANT-1-4 studies on patients with advanced, well differentiated NETs...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28275117/randomized-phase-ii-trial-of-parsatuzumab-anti-egfl7-or-placebo-in-combination-with-folfox-and-bevacizumab-for-first-line-metastatic-colorectal-cancer
#14
Rocío García-Carbonero, Eric van Cutsem, Fernando Rivera, Jacek Jassem, Ira Gore, Niall Tebbutt, Fadi Braiteh, Guillem Argiles, Zev A Wainberg, Roel Funke, Maria Anderson, Bruce McCall, Mark Stroh, Eric Wakshull, Priti Hegde, Weilan Ye, Daniel Chen, Ilsung Chang, Ina Rhee, Herbert Hurwitz
LESSONS LEARNED: These negative phase II results for parsatuzumab highlight the challenges of developing an agent intended to enhance the efficacy of vascular endothelial growth factor inhibition without the benefit of validated pharmacodynamic biomarkers or strong predictive biomarker hypotheses.Any further clinical development of anti-EGFL7 is likely to require new mechanistic insights and biomarker development for antiangiogenic agents. BACKGROUND: EGFL7 (epidermal growth factor-like domain 7) is a tumor-enriched vascular extracellular matrix protein that supports endothelial cell survival...
April 2017: Oncologist
https://www.readbyqxmd.com/read/28246006/efficacy-of-bevacizumab-therapy-in-recurrent-malignant-gliomas-in-relation-to-the-prior-recurrence-pattern-or-tumor-location
#15
Masahide Matsuda, Eiichi Ishikawa, Tetsuya Yamamoto, Hiroyoshi Akutsu, Shingo Takano, Akira Matsumura
Although promising preliminary results have been widely observed with bevacizumab for recurrent malignant gliomas, many unanswered questions remain to be resolved to achieve an optimal outcome. No predictive biomarkers of a survival benefit from bevacizumab have been established, and no consensus exists about the response or survival benefit regarding the prior recurrence pattern or tumor location. Here we retrospectively analyzed the clinical benefit from bevacizumab for recurrent malignant gliomas in relation to the prior recurrence pattern or tumor location...
February 25, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28209746/a-phase-ii-randomized-trial-go27827-of-first-line-folfox-plus-bevacizumab-with-or-without-the-met-inhibitor-onartuzumab-in-patients-with-metastatic-colorectal-cancer
#16
Johanna C Bendell, Howard Hochster, Lowell L Hart, Irfan Firdaus, Joseph R Mace, Joshua J McFarlane, Mark Kozloff, Daniel Catenacci, Jessie J Hsu, Stephen P Hack, David S Shames, See-Chun Phan, Hartmut Koeppen, Allen L Cohn
BACKGROUND: Dysregulated hepatocyte growth factor/mesenchymal-epithelial transition (MET) signaling is associated with poor prognosis and resistance to vascular endothelial growth factor inhibition in metastatic colorectal cancer (mCRC). We report outcomes from a double-blind, multicenter phase II trial of the MET inhibitor onartuzumab in combination with mFOLFOX-6 and bevacizumab for mCRC (GO27827; NCT01418222). MATERIALS AND METHODS: Patients were randomized 1:1 to receive onartuzumab (10 mg/kg intravenously [IV]) or placebo plus mFOLFOX-6 and bevacizumab (5 mg/kg IV)...
March 2017: Oncologist
https://www.readbyqxmd.com/read/28188101/antiangiogenic-therapy-in-advanced-non-small-cell-lung-cancer-a-meta-analysis-of-phase-iii-randomized-trials
#17
REVIEW
Jacques Raphael, Kelvin Chan, Safiya Karim, Robert Kerbel, Henry Lam, Keemo Delos Santos, Ronak Saluja, Sunil Verma
We conducted a meta-analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non-small-cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology. and AT dose. Pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and pooled odds ratio (OR) for overall response rates (RR) were calculated...
January 12, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28162945/postoperative-adjuvant-systemic-therapy-in-completely-resected-non-small-cell-lung-cancer-a-systematic-review
#18
REVIEW
Penelope Bradbury, Duvaraga Sivajohanathan, Adrien Chan, Swati Kulkarni, Yee Ung, Peter M Ellis
The purpose of the present review was to determine whether the use of postoperative adjuvant systemic therapy in patients with completely resected non-small-cell lung cancer (NSCLC) improves survival. Cancer Care Ontario's Program in Evidence-Based Care reviewed the evidence to update previously published recommendations for patients with completely resected NSCLC. Relevant studies were identified from a systematic MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews search of studies published from 2010 to 2016...
July 12, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28129643/il-8-and-enos-polymorphisms-predict-bevacizumab-based-first-line-treatment-outcomes-in-ras-mutant-metastatic-colorectal-cancer-patients
#19
Mariantonietta Di Salvatore, Filippo Pietrantonio, Armando Orlandi, Marzia Del Re, Rosa Berenato, Ernesto Rossi, Marta Caporale, Donatella Guarino, Antonia Martinetti, Michele Basso, Roberta Mennitto, Concetta Santonocito, Alessia Mennitto, Giovanni Schinzari, Ilaria Bossi, Ettore Capoluongo, Romano Danesi, Filippo de Braud, Carlo Barone
BACKGROUND: Predictive biomarkers of efficacy and toxicity of bevacizumab have not yet been validated. This study assessed the influence of IL-8, eNOS and VEGF-A polymorphisms in RAS mutated metastatic colorectal cancer patients receiving bevacizumab-based chemotherapy. METHODS: 120 patients treated with first-line combination FOLFOX6 plus bevacizumab were included. A historical cohort of 112 RAS mutated colorectal cancer patients treated with FOLFOX6 alone served as control group...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28068936/retrospective-study-of-ras-pik3ca-braf-tumor-mutations-as-predictors-of-response-to-first-line-chemotherapy-with-bevacizumab-in-metastatic-colorectal-cancer-patients
#20
Izuma Nakayama, Eiji Shinozaki, Tomohiro Matsushima, Takeru Wakatsuki, Mariko Ogura, Takashi Ichimura, Masato Ozaka, Daisuke Takahari, Mitsukuni Suenaga, Keisho Chin, Nobuyuki Mizunuma, Kensei Yamaguchi
BACKGROUND: After analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer...
January 9, 2017: BMC Cancer
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