ArticleOncotarget2016
Carcinoma-associated fibroblasts affect sensitivity to oxaliplatin and 5FU in colorectal cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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, 55 citations in OpenAlex.
- Article
- Mitochondrial Metabolic Reprogramming in Colorectal Cancer-Associated Fibroblasts: An Up-to-Date Review.Cancers · 2026Review
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- Artificial intelligence applications in oxaliplatin-based chemotherapy for colon cancer: advancing prognosis, toxicity prediction, and dose personalization.Frontiers in pharmacology · 2026Review
- Prognostic implications of cancer-associated fibroblasts and desmoplastic reaction in stage III colon cancer risk groups.Future oncology (London, England) · 2025Article
- Unveiling the tumor microenvironment in colorectal cancer therapeutic resistance.Frontiers in cell and developmental biology · 2025Review
- Probing the Depths of Molecular Complexity: STAT3 as a Key Architect in Colorectal Cancer Pathogenesis.Current gene therapy · 2025Review
- Drug-Resistance Biomarkers in Patient-Derived Colorectal Cancer Organoid and Fibroblast Co-Culture System.Current issues in molecular biology · 2024Article
- The Critical Function of microRNAs in Developing Resistance against 5- Fluorouracil in Cancer Cells.Mini reviews in medicinal chemistry · 2024Review
- A WGCNA-based cancer-associated fibroblast risk signature in colorectal cancer for prognosis and immunotherapy response.Translational cancer research · 2023Article
- Review
- Cancer-Associated Fibroblasts: The Origin, Biological Characteristics and Role in Cancer-A Glance on Colorectal Cancer.Cancers · 2022Review
- Cancer-associated fibroblasts in colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Article
- Cancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action.Frontiers in oncology · 2022Review
- [Research Progress in Immunosuppressive Tumor Microenvironment of Gastrointestinal Cancer].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Review
- Tumour immune microenvironment biomarkers predicting cytotoxic chemotherapy efficacy in colorectal cancer.Journal of clinical pathology · 2021Review
- Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment.Biology · 2021Review
- Targeting STAT3 Signaling Pathway in Colorectal Cancer.Biomedicines · 2021Review
- Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.Signal transduction and targeted therapy · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The importance of tumor microenvironment (TME) as a relevant contributor to cancer progression and its role in the development of de novo resistance to targeted therapies has become increasingly apparent. However, the mechanisms of microenvironment-mediated drug resistance for nonspecific conventional chemotherapeutic agents, such as platinum compounds or antimetabolites, are still unclear.Here we describe a mechanism induced by soluble factors released by carcinoma-associated fibroblasts (CAFs) that induce the translocation of AKT, Survivin and P38 to the nucleus of tumor cells. These changes are guided to ensure DNA repair and the correct entrance and exit from mitosis in the presence of chemotherapy. We used conditioned media (CM) from normal-colonic fibroblasts and paired CAFs to assess dose response curves of oxaliplatin and 5-fluorouracil, separately or combined, compared with standard culture medium. We also evaluated a colony-forming assay and cell death to demonstrate the protective role of CAF-CM. Immunofluorescence confirmed the translocation of AKT, P38 and Survivin to the nucleus induced by CAF-soluble factors. We also have shown that STAT3 or P38 inhibition provides a promising strategy for overcoming microenvironment-mediated resistance. Conversely, pharmacologic AKT inhibition induces an antagonistic effect that relieves a cMET and STAT3-mediated compensatory feedback that might explain the failure of AKT inhibitors in the clinic so far.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.