ArticleScientific reports2021
Chemotherapy confers a conserved secondary tolerance to EGFR inhibition via AXL-mediated signaling bypass.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Single-Cell RNA-Sequencing Reveals Tumor Microenvironment Composition and Prior Therapy Modulate Response to Axl Inhibition.Cellular and molecular bioengineering · 2026Article
- Endophytic Aspergillus glaucus as a novel epothilone B producer: Antiproliferative activity and in silico analysis.Applied microbiology and biotechnology · 2026Article
- EGFR-to-Src family tyrosine kinase switching in proliferating-DTP TNBC cells creates a hyperphosphorylation-dependent vulnerability to EGFR TKI.Cancer cell international · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Axl inhibitor-mediated reprogramming of the myeloid compartment of theFrontiers in immunology · 2025Article
- Evaluation of the Role of AXL in Fusion-positive Pediatric Rhabdomyosarcoma Identifies the Small-molecule Inhibitor Bemcentinib (BGB324) as Potent Chemosensitizer.Molecular cancer therapeutics · 2024Article
- Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research.Discover nano · 2024Review
- EGFR bypass activation mediates acquired resistance to regorafenib in hepatocellular carcinoma.Frontiers in medicine · 2024Article
- Article
- Complement inhibitor CSMD1 modulates epidermal growth factor receptor oncogenic signaling and sensitizes breast cancer cells to chemotherapy.Journal of experimental & clinical cancer research : CR · 2021Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance remains the major culprit of therapy failure in disseminated cancers. Simultaneous resistance to multiple, chemically different drugs feeds this failure resulting in cancer relapse. Here, we investigate co-resistance signatures shared between antimitotic drugs (AMDs) and inhibitors of receptor tyrosine kinases (RTKs) to probe mechanisms of secondary resistance. We map co-resistance ranks in multiple drug pairs and identified a more widespread occurrence of co-resistance to the EGFR-tyrosine kinase inhibitor (TKI) gefitinib in hundreds of cancer cell lines resistant to at least 11 AMDs. By surveying different parameters of genomic alterations, we find that the two RTKs EGFR and AXL displayed similar alteration and expression signatures. Using acquired paclitaxel and epothilone B resistance as first-line AMD failure models, we show that a stable collateral resistance to gefitinib can be relayed by entering a dynamic, drug-tolerant persister state where AXL acts as bypass signal. Delayed AXL degradation rendered this persistence to become stably resistant. We probed this degradation process using a new EGFR-TKI candidate YD and demonstrated that AXL bypass-driven collateral resistance can be suppressed pharmacologically. The findings emphasize that AXL bypass track is employed by chemoresistant cancer cells upon EGFR inhibition to enter a persister state and evolve resistance to EGFR-TKIs.
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