ArticleCancer research2014
Oncogenic KRAS confers chemoresistance by upregulating NRF2.
Article in Cancer research, 2014. 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 188 papers.
What it found
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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.
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Who cites it
188 citing papers in PubMed, 288 citations in OpenAlex.
- Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016Trial
- The interplay between vitamin D3 and Nrf2 signaling: mechanistic insights and therapeutic potentials.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer.The EMBO journal · 2026Article
- Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).Cell communication and signaling : CCS · 2026Review
- Target choice and exon skipping regulate CRISPR-directed gene editing of NRF2 in head/neck and esophageal cancer cells.Molecular therapy. Oncology · 2026Article
- From metabolism to genome integrity: NRF2 as a key mediator of cancer therapy response.Frontiers in cell and developmental biology · 2026Review
- Pharmacokinetics and nephrotoxicity of cisplatin modulated by combination therapy with brusatol.Frontiers in pharmacology · 2026Article
- NRF2 as a ferroptosis gatekeeper in colorectal cancer: implications for therapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Involvement of KEAP1/NRF2 pathway in non-BRAF mutated squamous cell carcinoma of the thyroid.The Journal of pathology · 2025Article
- Differential Response and Resistance to KRAS-Targeted Therapy.Molecular carcinogenesis · 2025Review
- Thirty years of NRF2: advances and therapeutic challenges.Nature reviews. Drug discovery · 2025Review
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
- Decoding the NRF2-NOTCH Crosstalk in Lung Cancer-An Update.Antioxidants (Basel, Switzerland) · 2025Review
- ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review).Oncology letters · 2025Review
- Article
- Bone-derived nanoparticles (BNPs) enhance osteogenic differentiationNanoscale advances · 2025Article
- Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.Biomedicines · 2025Review
- Regulation of SLC7A11 as an unconventional checkpoint in tumorigenesis through ferroptosis.Genes & diseases · 2025Review
- Repurposing dimethyl fumarate for cancer therapy: current evidence and future directions.Frontiers in pharmacology · 2025Review
128 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Oncogenic KRAS mutations found in 20% to 30% of all non-small cell lung cancers (NSCLC) are associated with chemoresistance and poor prognosis. Here we demonstrate that activation of the cell protective stress response gene NRF2 by KRAS is responsible for its ability to promote drug resistance. RNAi-mediated silencing of NRF2 was sufficient to reverse resistance to cisplatin elicited by ectopic expression of oncogenic KRAS in NSCLC cells. Mechanistically, KRAS increased NRF2 gene transcription through a TPA response element (TRE) located in a regulatory region in exon 1 of NRF2. In a mouse model of mutant KrasG12D-induced lung cancer, we found that suppressing the NRF2 pathway with the chemical inhibitor brusatol enhanced the antitumor efficacy of cisplatin. Cotreatment reduced tumor burden and improved survival. Our findings illuminate the mechanistic details of KRAS-mediated drug resistance and provide a preclinical rationale to improve the management of lung tumors harboring KRAS mutations with NRF2 pathway inhibitors.
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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.