E-BiTS study
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 78988 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: A: FTD/TPI monotherapy
FTD/TPI (35 mg/m2 given orally twice daily on days 1-5 and 8-12 in a 28-day cycle)
B: Bi-weekly FTD/TPI+BEV combination
Bi-weekly FTD/TPI (35 mg/m2 given orally twice daily on days 1-5 in a 14-day cycle) with BEV (5 mg/kg on day1, every 2 weeks)
Primary outcome(s): Overall survival
Study Design: randomized controlled trial, open(masking not used), active control, parallel assignment, treatment purpose
| 2614546 | ecrin-mdr-crc
Project description:Integrative analysis of colorectal cancer (CRC) whole genomes and matched transcriptomes revealed that somatic promoter mutations are associated with increased Chromodomain helicase DNA-binding protein 2 (CHD2) levels. In both primary and metastatic CRC patients, elevated CHD2 levels are associated with worse prognosis and overall survival. We find that CHD2 increases promoter-transcription start site-chromatin accessibility and transcriptional upregulation of multiple oncogenes. In vitro, elevated CHD2 promoted CRC cell proliferation, migration and growth. In orthotopic xenografts, CHD2 promoted higher tumor burden and abdominal metastases, most prominently to the liver. FTD/TPI is an FDA approved chemotherapy for advanced chemo-refractory CRC. In orthotopic CRC models, FTD/TPI was highly effective in reducing metastases and prolonging survival for CHD2 high expressing CRCs. Thus, high CHD2 expression may be a potential CRC chemopredictive biomarker for FTD/TPI. Overall, these results provide new insights into the role of non-coding mutations and CHD2 levels to promote CRC growth and metastasis.
2021-02-12 | GSE146398 | GEO
Project description:Primary outcome(s): Overall survival (OS) of sequential treatment with regorafenib-FTD/TPI
| 2655323 | ecrin-mdr-crc
Project description:Collection of real world data on the clinical efficacy of trifluridine/ tipiracil (FTD/TPI) in the Greek population.
| 2383608 | ecrin-mdr-crc
Project description:Background. Late-line treatment in metastatic colorectal cancer (mCRC) can improve the prognosis. However, not every patient has a benefit and may experience severe side effects. Thus, predictive/prognostic biomarkers are urgently needed. Despite many promising results, the role of circulating tumor DNA (ctDNA) analysis in trifluridin/tipiracil (FTD/TPI) treated mCRC patients is so far still elusive.
Study design. This prospective non-interventional translational biomarker phase II study enrolled 30 metastatic CRC patients treated with FTD/TPI. The primary study aim was to identify a molecular biomarker to predict overall survival (OS) benefit upon FTD/TPI treatment.
Methods. mCRC patients (60% male, 40% female) with FTD/TPI therapy were included. Molecular profiling in cell-free DNA from plasma was performed prior to treatment and on average 4, 8 and 12 weeks after FTD/TPI initiation. Tumor levels were assessed as the highest variant allele frequency (hVAF) and correlated with OS. Uni- and multivariate analyses for survival were performed with clinical variables. Multivariate analyses for survival and treatment efficacy were adjusted to age, gender and ECOG performance status.
Results. Compared to previous data, our disease control rate of 30% was lower with a median OS of 8.1 months and a median PFS of 3.2 months. At baseline (BL) and the first two follow-ups (FU), a hVAF cut-off of 7.5% was most discriminative (BL HR 0.39 95% CI 0.16 - 0.98 P=0.0212, FU1 HR 0.30 95% CI 0.12 -0.77 P=0.0021, FU2 HR 0.23 95% CI 0.08-0.70 P=0.0004) whereas at the last follow-up the stratification was most pronounced at a 15% cut-off. An elevated hVAF trajectory over time was associated with a higher risk of death.
Conclusion. ctDNA is detectable in a high proportion of mCRC patients. Changes in ctDNA levels are associated with survival among FTD/TPI therapy and may identify patients who benefit most from treatment in these late-stage disease.
| EGAS00001006883 | EGA
Project description:Background and study aims
Worldwide, nearly 1.25 million patients are diagnosed with colorectal cancer each year. At least 50% of patients develop metastases, and most of these patients have unresectable tumours (unable to be removed). Standard treatment for these patients involves chemotherapy and monoclonal antibodies targeting vascular endothelial growth factor (VEGF the cells that stimulate formation of blood vessels). In patients with KRAS wild-type tumours (abnormal tumours), monoclonal antibodies targeting epidermal growth factor receptor (EGFR which stimulates cell growth) are also used. 5-year survival rates in patients with metastatic colorectal cancer (mCRC), representing Stage IV CRC, were reached by only about 15% of mCRC patients. Although the outcome of patients with mCRC has clearly improved during recent years with median survival now reaching more than 30 months in recent clinical trials, more treatment options are needed for patients with disease progression after fluoropyrimidine (e.g. 5-FU), irinotecan, oxaliplatin, applicable anti-VEGF agents and anti-EGFR agents or those unable to tolerate these agents. Trifluridine/tipiracil (FTD/TPI; Lonsurf®) has been authorized in the EU since April 2016 for treatment of these patients. On the basis of the severity of the tumour disease with rather limited treatment options within the context of a previously treated tumour disease in the end-of-life situation, the health-related quality of life (HRQoL) is very important to describe the impact of treatment on the patient’s functioning regarding physical health (including disease-related morbidity), social, emotional, cognitive and role aspects. Changes of HRQoL during and after treatment with FTD/TPI have not been investigated so far in clinical trials. The aim of this study is to investigate the HRQoL in patients treated with FTD/TPI and those who are treated with best-supportive-care (BSC) while being suitable for treatment with FTD/TPI according to the summary of product characteristics.
Who can participate?
Adults aged 18 and older who have colorectal cancer.
What does the study involve?
Participants who are eligible for FTD/TPI therapy are treated like mCRC cancer patients in regular medical service receiving FTD/TPI with the only exemption that these cancer patients have to fill out 2 questionnaires (in total 36 questions) concerning their quality of life at treatment baseline and at the end of each FTD/TPI treatment cycle until end-of-treatment (i.e. disease progression).
| 2425712 | ecrin-mdr-crc
Project description:The combination of FOLFOX and bevacizumab (FOLFOX-Bev) is a promising treatment for advanced colorectal cancer (CRC). To gain insights into the cellular changes associated with FOLFOX-Bev treatment, we conducted single-cell transcriptomic analysis of CRC samples derived from a patient before and after treatment. Our results show that cancer cells with high proliferative, metastatic, and pro-angiogenic properties respond better to FOLFOX-Bev treatment. Moreover, FOLFOX-Bev enhances CD8+ T cell cytotoxicity, thereby boosting the anti-tumor immune response. Conversely, FOLFOX-Bev impairs the functionality of tumor-associated macrophages, plasma cells, and cancer-associated fibroblasts, leading to a decrease in VEGFB-mediated angiogenesis. Furthermore, FOLFOX-Bev treatment reset intercellular communication, which could potentially affect the function of non-cancer cells. Our findings provide valuable insights into the molecular mechanisms underlying the response of advanced CRC to FOLFOX-Bev treatment and highlight potential targets for improving the efficacy of this treatment strategy.
2023-07-20 | GSE232525 | GEO
Project description:Background and aims: Trichosanthis Pericarpium injection (TPI) produces a significant effect on regulating lipid metabolism and antioxidation, whose effects on non-alcoholic fatty liver disease (NAFLD) still remain unclear. In this study, we delved into the pharmacological functions of TPI on NAFLD and its underlying mechanisms. Methods: NAFLD mice model was induced by administering a high-fat diet (HFD) for 12 weeks, followed by intraperitoneal injection of TPI for 4 weeks. Concurrently, to explore the potential mechanisms, we utilized AML12 cells exposed to oleic acid (OA) as an in vitro model. Non target metabolomics and transcriptomics were used to explore the mechanism by which TPI improves lipid metabolism in mouse liver. Results: Our findings indicate that TPI significantly improved metabolic abnormalities and hepatic fat deposition in HFD mice. TPI treatment also yielded analogous results in AML12 cells treated with OA. Metabolomic analysis revealed alterations in metabolites in NAFLD mice, with ABC transporters exhibiting the most prominent changes. Further screening of gene changes related to this pathway showed a significant increase in ABCC5 expression in the NAFLD mice, while TPI treatment effectively reduced the expression level of ABCC5. Transcriptomic analysis demonstrated a marked increase in the expression of the transcription factor KLF6 in the NAFLD group, which positively correlated with ABCC5 expression. Further luciferase reporter gene experiments confirmed that KLF6 can directly regulate the expression of ABCC5, thereby affecting lipid metabolism and participating in the development of NAFLD. Notably, TPI treatment was able to reverse this process. Conclusions: In conclusion, TPI improves NAFLD by alleviating hepatic lipid metabolism dysregulation through the KLF6/ABCC5 pathway.
2024-07-29 | GSE273292 | GEO
Project description:The purpose of this study is to evaluate the combination of panitumumab and Triflridine/Tipiracil (FTD/TPI; TAS-102) in patients with RAS wild-type metastatic colorectal cancer (CRC) refractory to standard chemotherapy (oxaliplatin, fluoropyrimidines, irinotecan and angiogenesis inhibitors).
| 2202964 | ecrin-mdr-crc