ArticleCancer research2021
Hypoxia Drives Dihydropyrimidine Dehydrogenase Expression in Macrophages and Confers Chemoresistance in Colorectal Cancer.
Article in Cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Development and validation of a nomogram based on three-dimensional quantitative parameters from dual-layer detector spectral computed tomography for predicting treatment response to neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma.Journal of gastrointestinal oncology · 2026Article
- Article
- Targeting RPRD1B overcomes chemoresistance in gastric cancer by suppressing the TOPBP1-mediated DNA damage repair pathway.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Oncometabolites and Hypoxia-Regulated Exosomes Shape HIF-Driven Macrophage Programs Across Type 2 Diabetes, Atherosclerosis, and Cancer.International journal of molecular sciences · 2026Review
- GIPC1 Restrains the Progression and Chemoresistance of Colorectal Cancer by Regulating TTC7B/mTOR/NF-κB Axis.International journal of biological sciences · 2026Article
- SuperGLUE facilitates an explainable training framework for multi-modal data analysis.Cell reports methods · 2025Article
- Evaluation of induction chemotherapy response using multiphasic dual-energy CT in nasopharyngeal carcinoma.European radiology · 2025Article
- Living photosynthetic micro/nano-platforms: Engineering unicellular algae for biomedical applications.Bioactive materials · 2025Review
- Nomogram based on dual-energy computed tomography to predict the response to induction chemotherapy in patients with nasopharyngeal carcinoma: a two-center study.Cancer imaging : the official publication of the International Cancer Imaging Society · 2025Article
- Targeting tumor-associated macrophages in colon cancer: mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
- Investigating the role of MicroRNA-519d-3p in enhancing chemosensitivity of colorectal cancer cells to 5-Fluorouracil through PFKFB3 targeting.Clinics (Sao Paulo, Brazil) · 2025Article
- Natural compounds modulate the mechanism of action of tumour-associated macrophages against colorectal cancer: a review.Journal of cancer research and clinical oncology · 2024Review
- Research progress of tumor-associated macrophages in immune checkpoint inhibitor tolerance in colorectal cancer.World journal of gastrointestinal oncology · 2024Review
- Metabolic reprogramming of hypoxic tumor-associated macrophages through CSF-1R targeting favors treatment efficiency in colorectal cancers.Journal for immunotherapy of cancer · 2024Article
- Exploring Predictive and Prognostic Biomarkers in Colorectal Cancer: A Comprehensive Review.Cancers · 2024Review
- Novel hypoxia- and lactate metabolism-related molecular subtyping and prognostic signature for colorectal cancer.Journal of translational medicine · 2024Article
- HIF2α, Hepcidin and their crosstalk as tumour-promoting signalling.British journal of cancer · 2023Review
- A Brief Review on Chemoresistance; Targeting Cancer Stem Cells as an Alternative Approach.International journal of molecular sciences · 2023Review
- Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Unraveling Colorectal Cancer and Pan-cancer Immune Heterogeneity and Synthetic Therapy Response Using Cuproptosis and Hypoxia Regulators by Multi-omic Analysis and Experimental Validation.International journal of biological sciences · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal adenocarcinoma is a leading cause of death worldwide, and immune infiltration in colorectal tumors has been recognized recently as an important pathophysiologic event. In this context, tumor-associated macrophages (TAM) have been related to chemoresistance to 5-fluorouracil (5-FU), the first-line chemotherapeutic agent used in treating colorectal cancers. Nevertheless, the details of this chemoresistance mechanism are still poorly elucidated. In the current study, we report that macrophages specifically overexpress dihydropyrimidine dehydrogenase (DPD) in hypoxia, leading to macrophage-induced chemoresistance to 5-FU via inactivation of the drug. Hypoxia-induced macrophage DPD expression was controlled by HIF2α. TAMs constituted the main contributors to DPD activity in human colorectal primary or secondary tumors, while cancer cells did not express significant levels of DPD. In addition, contrary to humans, macrophages in mice do not express DPD. Together, these findings shed light on the role of TAMs in promoting chemoresistance in colorectal cancers and identify potential new therapeutic targets. SIGNIFICANCE: Hypoxia induces HIF2α-mediated overexpression of dihydropyrimidine dehydrogenase in TAMs, leading to chemoresistance to 5-FU in colon cancers.
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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.