ArticleOncoTargets and therapy2015
Positive feedback between oncogenic KRAS and HIF-1α confers drug resistance in colorectal cancer.
Article in OncoTargets and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers.
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
18 citing papers in PubMed, 20 citations in OpenAlex.
- Cytogenetic signatures favoring metastatic organotropism in colorectal cancer.Nature communications · 2025Article
- Impact of HIF-1α, LOX and ITGA5 Synergistic Interaction in the Tumor Microenvironment on Colorectal Cancer Prognosis.Diagnostics (Basel, Switzerland) · 2025Article
- Unveiling the role ofTranslational cancer research · 2024Article
- Anti-angiogenesis in colorectal cancer therapy.Cancer science · 2024Review
- Long-term proliferation of immature hypoxia-dependent JMML cells supported by a 3D in vitro system.Blood advances · 2023Article
- A microfluidic-based PDAC organoid system reveals the impact of hypoxia in response to treatment.Cell death discovery · 2023Article
- Evaluation of AMG510 Therapy onBioengineering (Basel, Switzerland) · 2022Article
- Review
- Non-canonical approaches to targeting hypoxic tumors.American journal of cancer research · 2022Review
- Comprehensive characterization of a drug-resistance-related ceRNA network across 15 anti-cancer drug categories.Molecular therapy. Nucleic acids · 2021Article
- Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage.Cell communication and signaling : CCS · 2021Review
- A Driver Never Works Alone-Interplay Networks of Mutant p53, MYC, RAS, and Other Universal Oncogenic Drivers in Human Cancer.Cancers · 2020Review
- Expression of pro-angiogenic factors as potential biomarkers in experimental models of colon cancer.Journal of cancer research and clinical oncology · 2020Article
- Hypoxia Induces Drug Resistance in Colorectal Cancer through the HIF-1α/miR-338-5p/IL-6 Feedback Loop.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Optimizing sequential treatment with anti-EGFR and VEGF mAb in metastatic colorectal cancer: current results and controversies.Cancer management and research · 2019Review
- High HIF-1α expression predicts poor prognosis of patients with colon adenocarcinoma.International journal of clinical and experimental pathology · 2018Article
- Mechanisms underlyingWorld journal of radiology · 2016Review
- Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
- Retracted
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 30%-50% of colorectal cancers (CRCs) harbor the somatic mutated KRAS gene. KRAS G12V, one of the most common KRAS mutations in CRCs, is linked to increased tumor aggressiveness, less response to anti-epidermal growth factor receptor (EGFR) therapy, and poor survival rate. In this study, we sought to determine whether resistance to EGFR inhibitors in colorectal cancer cells harboring KRAS G12V mutation is associated with hypoxia. Our data indicated that HIF-1α was induced by KRAS G12V signaling at transcription level. Hypoxia or HIF-1α overexpression could increase KRAS G12V activity. Therefore, a positive feedback between hypoxia and KRAS G12V activation was formed. Cetuximab, an EGFR inhibitor, which has a minor effect on KRAS-mutant CRCs, could effectively inhibit the proliferation of CRC cells harboring KRAS G12V mutation when combined with HIF-1α inhibitor PX-478. Our data indicated that hypoxia was involved in resistance to anti-EGFR therapy, and a combination therapy might be necessary for CRC patients with KRAS mutation.
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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.