ArticleOncogene2020
S6K1 blockade overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. 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, 55 citations in OpenAlex.
- FGFR1 but not S6K1/2 drives intrinsic BRAF inhibitor resistance in melanoma.Cell death discovery · 2026Article
- S6K1 overexpression enhances autophagy in breast cancer cells by inducing the translation of CLU.Chinese medical journal · 2026Article
- S6K1 Modulates STAT3 Activation to Promote Resistance to Radiotherapy in Lung Cancer.International journal of molecular sciences · 2026Article
- A NovelInternational journal of surgical pathology · 2025Article
- Article
- S6K1 is a Targetable Vulnerability in Tumors Exhibiting Plasticity and Therapy Resistance.International journal of biological sciences · 2025Article
- USP22 promotes gefitinib resistance and inhibits ferroptosis in non-small cell lung cancer by deubiquitination of MDM2.Thoracic cancer · 2024Article
- High-throughput neural stem cell-based drug screening identifies S6K1 inhibition as a selective vulnerability in sonic hedgehog-medulloblastoma.Neuro-oncology · 2024Article
- HDAC1 and FOXK1 mediate EGFR-TKI resistance of non-small cell lung cancer through miR-33a silencing.Journal of translational medicine · 2024Article
- ELK1/MTOR/S6K1 Pathway Contributes to Acquired Resistance to Gefitinib in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Article
- Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression.American journal of cancer research · 2024Article
- Drug mechanism enrichment analysis improves prioritization of therapeutics for repurposing.BMC bioinformatics · 2023Article
- A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer.Vaccines · 2023Review
- Emerging roles of PHLPP phosphatases in lung cancer.Frontiers in oncology · 2023Review
- Roles of NExperimental hematology & oncology · 2022Review
- Article
- ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- The Potential Biological Roles and Clinical Significance of Anaphase-Promoting Complex Subunit 1 in Colorectal Cancer.Cancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
The development of resistance to EGFR Tyrosine kinase inhibitors (TKIs) in NSCLC with activating EGFR mutations is a critical limitation of this therapy. In addition to genetic alterations such as EGFR secondary mutation causing EGFR-TKI resistance, compensatory activation of signaling pathways without interruption of genome integrity remains to be defined. In this study, we identified S6K1/MDM2 signaling axis as a novel bypass mechanism for the development of EGFR-TKI resistance. The observation of S6K1 as a candidate mechanism for resistance to EGFR TKI therapy was investigated by interrogation of public databases and a clinical cohort to establish S6K1 expression as a prognostic/predictive biomarker. The role of S6K1 in TKI resistance was determined in in vitro gain-and-loss of function studies and confirmed in subcutaneous and orthotopic mouse lung cancer models. Blockade of S6K1 by a specific inhibitor PF-4708671 synergistically enhanced the efficacy of TKI without showing toxicity. The mechanistic study showed the inhibition of EGFR caused nuclear translocation of S6K1 for binding with MDM2 in resistant cells. MDM2 is a downstream effector of S6K1-mediated TKI resistance. Taken together, we present evidence for the reversal of resistance to EGFR TKI by the addition of small molecule S6K1/MDM2 antagonists that could have clinical benefit.
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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.