Angiopredict: predicting response for bevacizumab treatment
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001002724 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:In ANGIOPREDICT, academic cancer biologists and industry-based biotechnology researchers will work together with clinicians to identify biomarkers to predict whether individual metastatic colorectal cancer patients will respond positively to Avastin® combination therapy. Diagnostic tests using these biomarkers will also be developed to provide clinicians with the means to predict patient treatment responses in the future.
| EGAS00001005423 | EGA
Project description:Objective: Insights about differences in tumor vasculature and how it reacts to VEGF inhibition is limited, but nevertheless of major relevance to anti-angiogenic therapy. In this study we therefore characterize the effect of bevacizumab combined with chemoradiotherapy (CRT), and explore molecular and genetic markers for response prediction to this combination treatment. Material and Methods: In an academic multicentric randomized phase II study, patients with advanced rectal cancer have been treated with bevacizumab (5mg/kg) in combination with capecitabine (1650mg/m2/day) and radiotherapy (45Gy; 1.8Gy/day) with (50mg/m2) or without oxaliplatin prior to surgery. Of 59 patients, tumor tissue and blood samples were collected before treatment and after the first loading dose of bevacizumab but before CRT (week 3). First, cDNA micro-arrays were performed on the biopsies to investigate differences in gene expression of tumors from patients with and without a pathological complete response (pCR) before start of treatment and to identify biological processes affected by bevacizumab delivery. The paraffin embedded tissue was stained for blood vessels (CD31/CD34) combined with α-SMA (pericytes) and CA-IX (hypoxia). To explore candidate blood-based biomarkers ELISA’s were performed for PDGF-AA, PDGF-BB, THBS-1, IL-8, CYR61 and Ang-2. The expression of all markers was correlated with the pathological response of the patients. Results: Differences in tumoral gene expression are observed between patients with and without a pCR, with the first response group presenting a more angiogenic phenotype before start of treatment and changes in angiogenic processes after bevacizumab delivery. One dose of bevacizumab leads to a decrease in the number of pericyte covered blood vessels, a decrease in circulating PDGF-AA, PDGF-BB and Thrombospondin-1. Patients showing a pCR having less pericyte covered blood vessels, more hypoxia, and less circulating PDGF-BB compared to patients who did not have a pCR after bevacizumab treatment with chemoradiation and bevacizumab. Conclusions: The translational data demonstrate that tumors with an angiogenic expression profile respond better to bevacizumab combined with CRT and points towards a possible role for PDGF, CA-IX and pericyte covered blood vessels for the early response prediction to this treatment. Our findings suggest a role for mural cell recruitment and vessel maturation for the susceptibility of the tumor vasculature to bevacizumab treatment. Further validation of our biological observations and hypothesis generating data in randomized trials is needed.
2016-08-02 | GSE60331 | GEO
Project description:Objective: Insights about differences in tumor vasculature and how it reacts to VEGF inhibition is limited, but nevertheless of major relevance to anti-angiogenic therapy. In this study we therefore characterize the effect of bevacizumab combined with chemoradiotherapy (CRT), and explore molecular and genetic markers for response prediction to this combination treatment. Material and Methods: In an academic multicentric randomized phase II study, patients with advanced rectal cancer have been treated with bevacizumab (5mg/kg) in combination with capecitabine (1650mg/m2/day) and radiotherapy (45Gy; 1.8Gy/day) with (50mg/m2) or without oxaliplatin prior to surgery. Of 59 patients, tumor tissue and blood samples were collected before treatment and after the first loading dose of bevacizumab but before CRT (week 3). First, cDNA micro-arrays were performed on the biopsies to investigate differences in gene expression of tumors from patients with and without a pathological complete response (pCR) before start of treatment and to identify biological processes affected by bevacizumab delivery. The paraffin embedded tissue was stained for blood vessels (CD31/CD34) combined with α-SMA (pericytes) and CA-IX (hypoxia). To explore candidate blood-based biomarkers ELISAâs were performed for PDGF-AA, PDGF-BB, THBS-1, IL-8, CYR61 and Ang-2. The expression of all markers was correlated with the pathological response of the patients. Results: Differences in tumoral gene expression are observed between patients with and without a pCR, with the first response group presenting a more angiogenic phenotype before start of treatment and changes in angiogenic processes after bevacizumab delivery. One dose of bevacizumab leads to a decrease in the number of pericyte covered blood vessels, a decrease in circulating PDGF-AA, PDGF-BB and Thrombospondin-1. Patients showing a pCR having less pericyte covered blood vessels, more hypoxia, and less circulating PDGF-BB compared to patients who did not have a pCR after bevacizumab treatment with chemoradiation and bevacizumab. Conclusions: The translational data demonstrate that tumors with an angiogenic expression profile respond better to bevacizumab combined with CRT and points towards a possible role for PDGF, CA-IX and pericyte covered blood vessels for the early response prediction to this treatment. Our findings suggest a role for mural cell recruitment and vessel maturation for the susceptibility of the tumor vasculature to bevacizumab treatment. Further validation of our biological observations and hypothesis generating data in randomized trials is needed. This study involves samples of patients enrolled in the AXEbeam trail that were analysed by Primeview microarray (Affymetrix). Biopsies were taken at two different timepoints: before treatment (tumor and normal mucosa) and after the first loading dose of bevacizumab but before chemoradiation (only tumor, week 3). Patients were classified into two groups: with a complete pathological response at time of surgery (Responders=R) or non-responders (NR). For the responders, we collected 21 samples in total (7 tumor samples and 8 normal mucosa samples taken before treatment and 6 tumor samples collected at week 3). From the non-responders we had 26 samples in total (9 tumor and 10 mucosa samples before treatment and 7 tumor samples at week 3 after a single dose of bevacizumab). Microarrays were run in two batches (15xxx versus 16xxx CEL file samples; indicated in the description field). Three samples (NJ 04/003 T1, RVS 09/002 M and NJ 04/003 W3) were put twice on the array (15897+16789; 15893+16790; 15898+16791) to verify and exclude batch effects. Please note that, due to these three technical repeats the total number of microarray CEL files is 50 (21 Responders, 26 Non-responders and 3 repeats).
2016-08-02 | E-GEOD-60331 | biostudies-arrayexpress
Project description:Purpose: To study the potential priming benefit of bevacizumab from subsequent immunotherapy (durvalumab) in advanced breast cancer patients Methods: We tested this hypothesis by adding durvalumab after progression to maintenance single-agent bevacizumab treatment in advanced HER2-negative patients (average 3 treatment lines). In order to study the potential priming benefit, patients had to experience disease progression while on bevacizumab maintenance prior to entering the trial. In addition, we sought to find traits in peripheral-blood mononuclear cells (PBMCs) and tumor biopsies that informed about this immuno-priming, in an attempt to search for novel biomarkers of efficacy of the combo and obtain a better understanding of the biology of this clinical scenario. Results: Patients that experienced clinical benefit, compared with the remaining patients, displayed a lymphocyte pattern in PBMCs consisting on increased T-effector subpopulations (CD4- and CD8- effector and effector-memory) and decreased immunosuppressive T-regulatory cells. Gene-expression studies in tumor samples showed a congruent pattern, with increased T-effector and memory T cell signatures in responders, and increased T-regulatory and decreased active dendritic cells in non-responders. These events were observed in patients that displayed vascular normalization features as a result of previous bevacizumab, supporting the immuno-priming effects of this strategy.
2020-10-15 | GSE139050 | GEO
Project description:Immuno-priming with bevacizumab: durvalumab plus bevacizumab after prolonged exposition to bevacizumab in breast cancer
| PRJNA578152 | ENA
Project description:TMT proteomics was used to detect the difference in protein expression of bevacizumab-resistant xenograft tumor tissue in nude mice.
2022-10-13 | PXD030202 | Pride
Project description:The combination of bevacizumab with temozolomide and radiotherapy was shown to prolong progression-free survival in newly diagnosed glioblastoma patients, and this emphasizes the potential of bevacizumab as a glioma treatment. However, while bevacizumab effectively inhibits angiogenesis, it has also been reported to induce invasive proliferation. This study examined gene expression in glioma cells to investigate the mechanisms of bevacizumab-induced invasion. We made a human glioma U87ΔEGFR cell xenograft model by stereotactically injecting glioma cells into the brain of animals. We administered bevacizumab intraperitoneally three times per week. At 18 days after tumor implantation, the brains were removed for histopathology and mRNA was extracted. In vivo, bevacizumab treatment increased glioma cell invasion. qRT-PCR array analysis were perfomed.
2019-02-07 | GSE126168 | GEO
Project description:To investigate the possible mechanism of bevacizumab resistance in ovarian cancer ,we examined the changes in gene expression of SKOV3 before and after bevacizumab intervention. Results provide insight into molecular mechanisms of acquired resistance to bevacizumab in ovarian cancer.
2023-12-31 | GSE165419 | GEO
Project description:The patients who underwent surgery for primary lesions were examined. All patients had metastatic or recurrent CRC and received bevacizumab therapy as first line or second line treatment. Responders and nonresponders were determined based on RECIST and confirmed by CT or MRI. Gene-expression profiles of primary CRC were determined using Human Genome GeneChip arrays U133. Colorectal cancer patients who had undergone surgical resection of colorectal cancer were studied. To identify molecular signatures to predict response to bevacizumab, gene expression profiles were compared between Reponder and Non-responder.
2013-01-03 | E-GEOD-19862 | biostudies-arrayexpress
Project description:Gene expression of bevacizumab-resistant HT-29 tumors vs untreated control
2016-09-08 | GSE86525 | GEO