Comprehensive molecular analysis to predict the efficacy of bevacizumab in patients with metastatic colorectal cancer
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PROVIDER: PRJEB51806 | ENA |
REPOSITORIES: ENA
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Project description:predict the efficacy of bevacizumab in patients with metastatic colorectal cancer
| PRJEB51947 | ENA
Project description:Background: The efficacy of FOLFIRI plus an antiangiogenesis biologic agent as 2nd line therapy for metastatic colorectal adenocarcinoma is limited. TAS-102 is a novel oral antimetabolite with a distinct mechanism of action from fluoropyrimidines. We evaluated the antitumor efficacy of TAS-102, irinotecan and bevacizumab in patients with pre-treated, advanced colorectal adenocarcinoma in a multicenter, phase II, single-arm study. Methods: Patients with advanced colorectal adenocarcinoma who had progressed after oxaliplatin and fluoropyrimidine and were eligible for treatment with bevacizumab were treated with irinotecan, bevacizumab, and TAS-102 in 28-day cycles. The primary endpoint was progression-free survival (PFS). Results: We enrolled 35 evaluable patients. The study was positive. The median PFS was 7.9 (90% CI 6.2-11.8) months (vs. 6 months in historical control, p=0.018). The median overall survival was 16.5 (90% CI 9.8-17.5) months. Sixty-seven percent of patients experienced grade 3 or higher treatment-related adverse events. The most common toxicities were hematological (neutropenia) and gastrointestinal (diarrhea, nausea, and vomiting). Conclusions: Irinotecan, TAS-102 and bevacizumab is an active 2nd line therapy for patients with metastatic colorectal adenocarcinoma. Neutropenia is common and can affect dose density/intensity mandating use of G-CSF. A randomized study versus standard of care therapy is warranted.
2024-08-26 | GSE275628 | 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:Determination of the ion channel and transporters gene expression profile of Bevacizumab-adapted colorectal adenocarcinoma cells HCT116
2023-01-02 | GSE221948 | GEO
Project description:BackgroundAlthough bevacizumab is an important treatment for metastatic colorectal cancer (CRC), not all patients with CRC benefit from it; in unselected patient populations, only modest survival benefits have been reported.MethodsWe evaluated clinical outcomes in 110 patients using comprehensive molecular characterization to identify biomarkers for a response to bevacizumab-containing treatment. The molecular analysis comprised whole-exome sequencing, ribonucleic acid sequencing, and a methylation array on patient tissues.ResultsGenomic and molecular characterization was successfully conducted in 103 patients. Six of 103 CRC samples were hypermutated, and none of the non-hypermutant tumors were microsatellite unstable. Among those 103 patients, 89 had adenocarcinoma (ADC), 15 were diagnosed with mucinous ADC, and six had signet-ring cell carcinoma (SRCC). Consensus molecular subtype (CMS) 2 was unique to ADC. Of the four SRCCs, two were CMS1, one was CMS4, and the other was CMS3. APC mutation status was a significantly enriched factor in responders to bevacizumab treatment. Fibroblast growth factor receptor (FGFR) 1/2 signaling was upregulated in non-responders, whereas cell cycle, transfer ribonucleic acid processing, nucleotide excision repair, and oxidative phosphorylation pathways were enriched in responders. In addition, IGF1 was differentially expressed in non-responders (log2 fold change = -1.43, p = 4.11 × 10-5, false discovery rate = 0.098), and FLT1 was highly methylated in non-responders (p = 7.55 × 10-3). When the molecular pathways were reanalyzed separately according to the backbone chemotherapy (FOLFOX vs. FOLFIRI), the significance of the molecular pathways varied according to the backbone chemotherapy.ConclusionsThis study sought a subset of CRC patients with a distinct clinical response to chemotherapy containing bevacizumab. Our results need to be validated in a large group of homogenous patient cohort and examined according to the different chemotherapy backbones to create personalized therapeutic opportunities in CRC.
| S-EPMC10513961 | biostudies-literature
Project description:Response to drug therapy in individual colorectal cancer (CRC) patients is associated with tumor biology. Here we describe the genomic landscape of tumor samples of a homogeneous well-annotated series of patients with metastatic CRC of two phase III clinical trials, CAIRO and CAIRO2. DNA copy number aberrations of 349 patients are determined. Within three treatment arms, 194 chromosomal sub-regions are associated with progression free survival PFS (uncorrected single-test p-values < 0.005). These sub-regions are filtered for effect on mRNA expression, using an independent data set from The Cancer Genome Atlas (TCGA) which returned 171 genes. Three chromosomal regions are associated with a significant difference in PFS between treatment arms with or without irinotecan. One of these regions, 6q16.1-q21, correlates in vitro with sensitivity to SN-38, the active metabolite of irinotecan. This genomic landscape of metastatic CRC reveals a number of DNA copy number aberrations associated with response to drug therapy. aCGH data of colorectal cancers of patients from 2 clinical trials (CAIRO, CAIRO2). 105 patients were treated with capecitabine first line (CAIRO arm A), 111 patients were treated with capecitabine and irinotecan first line (CAIRO arm B), and 133 patients were treated with capecitabine, oxaliplatin and bevacizumab (CAIRO2 arm A).
2014-11-14 | E-GEOD-36864 | biostudies-arrayexpress
Project description:Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer
| PRJNA413394 | ENA
Project description:Transcriptomic data of Bevacizumab-adapted colorectal adenocarcinoma cells HCT116
| PRJNA916900 | ENA
Project description:We examined how the immune microenvironment molds tumor evolution in a longitudinal dataset of colorectal cancer liver metastases. Through multiplexed analyses, the immune microenvironment exerts a strong selection pressure during treatment of CLM tumor. Increasing infiltration of T cell were associated with favorable outcomes and sensitive response to chemotherapy ± Bevacizumab. Activation of fatty acid metabolism, xenobiotic metabolism, insulin receptor signaling pathway and neutrophils infiltration were observed in progressive tumors. TCR diversity in response metastatic regions was significantly increased compared with non-responder. Bevacizumab containing regimen facilitated T cell infiltrating to the tumor microenvironment which might consequently benefit from checkpoint immunotherapy. In responding patients, mutation load from plasma were reduced from baseline, but changed slightly in tumor tissues. This integrative and comparative omics analysis provides a new paradigm for understanding the evolution and treatment resistance of colorectal cancer liver metastases, with implications for identifying ways to advance treatment regimen and monitoring treatment response of colorectal cancer liver metastases.
2020-03-08 | GSE136114 | GEO
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