ArticleOncogene2019
mTOR mediates a mechanism of resistance to chemotherapy and defines a rational combination strategy to treat KRAS-mutant lung cancer.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 54 citations in OpenAlex.
- Narciclasine enhances cisplatin-induced apoptotic cell death by inducing unfolded protein response-mediated regulation of NOXA and MCL1.Cellular & molecular biology letters · 2025Article
- Progress of KRAS G12C inhibitors in the treatment of refractory colorectal cancer and strategies for drug resistance response.Investigational new drugs · 2025Review
- Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer.Cell death and differentiation · 2025Article
- eIF4F-mediated dysregulation of mRNA translation in cancer.RNA (New York, N.Y.) · 2025Review
- CASTOR1 phosphorylation predicts poor survival in male patients with KRAS-mutated lung adenocarcinoma.Cell & bioscience · 2024Article
- KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways.Cells · 2024Review
- Identification of protein biomarkers for prediction of response to platinum-based treatment regimens in patients with non-small cell lung cancer.Molecular oncology · 2024Article
- Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer.Oncogene · 2024Article
- A multiomic investigation of lung adenocarcinoma molecular subtypes.Journal of the Chinese Medical Association : JCMA · 2024Article
- Genetic variants in LKB1/AMPK/mTOR pathway are associated with clinical outcomes of chemotherapy in non-small cell lung cancer.Thoracic cancer · 2022Article
- Article
- c-MYC-mediated TRIB3/P62Acta pharmaceutica Sinica. B · 2022Article
- Metabolic synthetic lethality by targeting NOP56 and mTOR in KRAS-mutant lung cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- A Breakthrough Brought about by Targeting KRASCancers · 2022Review
- ZDHHC22-mediated mTOR palmitoylation restrains breast cancer growth and endocrine therapy resistance.International journal of biological sciences · 2022Article
- High DHCR7 Expression Predicts Poor Prognosis for Cervical Cancer.Computational and mathematical methods in medicine · 2022Article
- Modified Gold Nanoparticles to Overcome the Chemoresistance to Gemcitabine in Mutant p53 Cancer Cells.Pharmaceutics · 2021Article
- STAT3 contributes to cisplatin resistance, modulating EMT markers, and the mTOR signaling in lung adenocarcinoma.Neoplasia (New York, N.Y.) · 2021Article
- Synergistic effects of FGFR1 and PLK1 inhibitors target a metabolic liability in KRAS-mutant cancer.EMBO molecular medicine · 2021Article
- The plasticity of mRNA translation during cancer progression and therapy resistance.Nature reviews. Cancer · 2021Review
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic KRAS mutations comprise the largest subset of lung cancer defined by genetic alterations, but in the clinic no targeted therapies are available that effectively control mutational KRAS activation. Consequently, patients with KRAS-driven tumors are routinely treated with cytotoxic chemotherapy, which is often transiently effective owing to development of drug resistance. In this study, we show that hyperactivated mammalian target of rapamycin (mTOR) pathway is a characteristic hallmark of KRAS-mutant lung adenocarcinoma after chemotherapy treatment, and that KRAS-mutant lung cancer cells rely on persistent mTOR signaling to resist chemotherapeutic drugs. Coherently, mTOR inhibition circumvents the refractory phenotype and restores sensitivity of resistant KRAS-mutant lung cancer cells to chemotherapy. Importantly, drug combinations of clinically approved mTOR inhibitors and chemotherapy drugs synergize in inhibiting cell proliferation of KRAS-mutant cancer cells in vitro and in vivo, and the efficacy of this combination treatment correlates with the magnitude of mTOR activity induced by chemotherapy alone. These results pinpoint mTOR as a mechanism of resistance to chemotherapy in KRAS-mutant lung cancer and validate a rational and readily translatable strategy that combines mTOR inhibitors with standard chemotherapy to treat KRAS-mutant adenocarcinoma, the most common and deadliest lung cancer subset.
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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.