ArticleeLife2021
An epigenetic switch regulates the ontogeny of AXL-positive/EGFR-TKi-resistant cells by modulating miR-335 expression.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02488408 (A Phase Ib/II Multicenter Open-label Study of BGB324 as a Single Agent and in Combination With Cytarabine or Decitabine in Patients With Acute Myeloid Leukemia or as a Single Agent in Patients With Myelodysplastic Syndrome), which is not on this map. Cited by 8 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.
A Phase Ib/II Multicenter Open-label Study of BGB324 as a Single Agent and in Combination With Cytarabine or Decitabine in Patients With Acute Myeloid Leukemia or as a Single Agent in Patients With Myelodysplastic Syndrome
Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- A fast-progressing orthotopic ovarian cancer model reveals synergistic antitumor effects of AXL-targeting nanobodies and Olaparib.Gynecologic oncology reports · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- The Intricate Web of MicroRNAs in Modulating EGFR-TKI Resistance in Non-Small Cell Lung Cancer: A Comprehensive Review.Cancer management and research · 2025Review
- TAM family kinases as therapeutic targets at the interface of cancer and immunity.Nature reviews. Clinical oncology · 2023Review
- miR-124 as a Liquid Biopsy Prognostic Biomarker in Small Extracellular Vesicles from NSCLC Patients.International journal of molecular sciences · 2023Article
- Challenges of EGFR-TKIs in NSCLC and the potential role of herbs and active compounds: From mechanism to clinical practice.Frontiers in pharmacology · 2023Review
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Targeting MERTK and AXL inCancers · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
Despite current advancements in research and therapeutics, lung cancer remains the leading cause of cancer-related mortality worldwide. This is mainly due to the resistance that patients develop against chemotherapeutic agents over the course of treatment. In the context of non-small cell lung cancers (NSCLC) harboring EGFR-oncogenic mutations, augmented levels of AXL and GAS6 have been found to drive resistance to EGFR tyrosine kinase inhibitors such as Erlotinib and Osimertinib in certain tumors with mesenchymal-like features. By studying the ontogeny of AXL-positive cells, we have identified a novel non-genetic mechanism of drug resistance based on cell-state transition. We demonstrate that AXL-positive cells are already present as a subpopulation of cancer cells in Erlotinib-naïve tumors and tumor-derived cell lines and that the expression of AXL is regulated through a stochastic mechanism centered on the epigenetic regulation of miR-335. The existence of a cell-intrinsic program through which AXL-positive/Erlotinib-resistant cells emerge infers the need of treating tumors harboring EGFR-oncogenic mutations upfront with combinatorial treatments targeting both AXL-negative and AXL-positive cancer cells.
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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.