Trial reportJournal of translational medicine2015
Tumour pharmacodynamics and circulating cell free DNA in patients with refractory colorectal carcinoma treated with regorafenib.
Trial report in Journal of translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 5 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Circulating tumour DNA and its clinical utility in predicting treatment response or survival in patients with metastatic colorectal cancer: a systematic review and meta-analysis.British journal of cancer · 2022Pooled it
- Genomic and epigenomic biomarkers in colorectal cancer: From diagnosis to therapy.Advances in cancer research · 2021Pooled it
- PET/CT-Based Response Evaluation in Cancer-a Systematic Review of Design Issues.Molecular imaging and biology · 2020Pooled it
- Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.The oncologist · 2017Pooled it
- Prognostic value of circulating tumor DNA in patients with colon cancer: Systematic review.PloS one · 2017Pooled it
- Circulating tumor DNA as a prognostic biomarker in metastatic colorectal cancer: Post-hoc analysis of treatment response and survival outcomes in the ALTER-C-002 study.Biomolecules & biomedicine · 2026Trial
- Monitoring levels of circulating cell-free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment.Molecular oncology · 2021Trial
- A higher ctDNA fraction decreases survival in regorafenib-treated metastatic colorectal cancer patients. Results from the regorafenib's liquid biopsy translational biomarker phase II pilot study.International journal of cancer · 2021Trial
- Total lesion glycolysis (TLG) as an imaging biomarker in metastatic colorectal cancer patients treated with regorafenib.European journal of nuclear medicine and molecular imaging · 2017Trial
- The role of methylation in pituitary neuroendocrine tumors current insights and emerging perspectives.Molecular biology reports · 2026Review
- Systematic review and meta-analysis of studies assessing circulating tumor DNA kinetics in metastatic colorectal cancer.ESMO gastrointestinal oncology · 2026Review
- Detection ofOncology research · 2026Article
- Recent Advancement in Drug Designing as Small Molecules in Targeted Cancer Therapy: Challenges and Future Directions.Current cancer drug targets · 2025Review
- Review
- Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams.Cancers · 2023Review
- Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer.Cancer research and treatment · 2023Article
- Role of Circulating Tumor DNA in Gastrointestinal Cancers: Current Knowledge and Perspectives.Cancers · 2021Review
- Review
- Association of emergence of new mutations in circulating tumuor DNA during chemotherapy with clinical outcome in metastatic colorectal cancer.BMC cancer · 2021Article
- Metachronous pulmonary and pancreatic metastases arising from sigmoid colon cancer: A case report.World journal of clinical cases · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRegorafenib, a multi-kinase inhibitor, is used in the treatment of patients with metastatic colorectal cancer refractory to standard therapy. However, this benefit was limited to 1.4 months improvement in overall survival, with more than half of patients experiencing grade 3 to 4 adverse events. We aim to elucidate the pharmacodynamic effects of regorafenib in metastatic colorectal cancer and discover potential biomarkers that may predict clinical benefit.
methodsPatients with metastatic colorectal adenocarcinoma refractory to standard therapy with tumours amenable to biopsy were eligible for the study. Regorafenib was administered orally at 160 mg daily for 3 out of 4 weeks with tumour assessment every 2 cycles. Metabolic response was assessed by FDG PET-CT scans (pre-treatment and day 15); paired tumour biopsies (pre-treatment and day 21 post-treatment) were sampled for immunohistochemistry and proteomic profiling analyses. Plasma circulating cell free DNA was quantified serially before and after treatment.
resultsThere were 2(6%) partial responses out of 35 patients, and 8(23%) patients had stable disease for more than 7 months. Adverse event profile was similar to reported data. Recurrent somatic mutations in K-RAS, PIK3CA and BRAF were detected in plasma circulating cell free DNA in 14 patients; some mutations were not found in archival tumour. Total plasma circulating cell free DNA inversely correlated with progression free survival (PFS), and presence of KRAS mutations associated with shorter PFS. Immunohistochemistry of pre- and post- treatment biopsies showed majority of patients had downregulation of phosphorylated-VEGFR2, podoplanin, phosphorylated-AKT, Ki-67 and upregulation of the MEK-ERK axis, phosphorylated-C-MET, phosphorylated-SRC, phosphorylated-STAT3 and phosphorylated-JUN. Proteomic analysis of fine needle tumour aspirates showed down-regulation of PI3K was associated with longer PFS.
conclusionPlasma circulating cell free DNA may yield potential predictive biomarkers of regorafenib treatment. Downregulation of the PI3K-AKT axis may be an important predictor of clinical benefit.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.