ArticleTranslational oncology2019
MYC Amplification as a Potential Mechanism of Primary Resistance to Crizotinib in ALK-Rearranged Non-Small Cell Lung Cancer: A Brief Report.
Article in Translational oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
35 citing papers in PubMed, 45 citations in OpenAlex.
- A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy.International journal of molecular sciences · 2023Trial
- MYC contributes to targeted therapy resistance in lung cancers driven by MET exon 14-skipping alteration.NPJ precision oncology · 2026Article
- ALK Inhibitor Response in NovelJTO clinical and research reports · 2026Article
- Isolation and typing techniques for circulating tumor cells.Biomarker research · 2026Review
- Mechanisms of Resistance to ALK Inhibitors and Corresponding Treatment Strategies in Lung Cancer.International journal of general medicine · 2025Review
- Advances of nanopore direct sequencing technology and bioinformatics analysis for cell-free DNA detection and its clinical applications in cancer liquid biopsy.Frontiers in molecular biosciences · 2025Review
- The Use of Anaplastic Lymphoma Kinase Inhibitors in Non-Small-Cell Lung Cancer Treatment-Literature Review.Biomedicines · 2024Review
- Clinical difference on the variants and co-mutation in a Chinese cohort with ALK-positive advanced non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- ALK-tyrosine kinase inhibitor intrinsic resistance due toTranslational lung cancer research · 2024Article
- Recurrent mutations in tumor suppressorScience advances · 2024Article
- ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer.Molecular biomedicine · 2022Review
- MYC amplification-conferred primary resistance to capmatinib in aTranslational lung cancer research · 2022Article
- Alternative Treatment Options to ALK Inhibitor Monotherapy for EML4-ALK-Driven Lung Cancer.Cancers · 2022Review
- MYC Promotes Tyrosine Kinase Inhibitor Resistance in ROS1-Fusion-Positive Lung Cancer.Molecular cancer research : MCR · 2022Article
- Enhancer RNA AL928768.3 from the IGH Locus Regulates MYC Expression and Controls the Proliferation and Chemoresistance of Burkitt Lymphoma Cells with IGH/MYC Translocation.International journal of molecular sciences · 2022Article
- Review of Therapeutic Strategies for Anaplastic Lymphoma Kinase-Rearranged Non-Small Cell Lung Cancer.Cancers · 2022Review
- Article
- An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.Bosnian journal of basic medical sciences · 2022Review
- Clinical Applications of Circulating Tumour Cells and Circulating Tumour DNA in Non-Small Cell Lung Cancer-An Update.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionTranslocations of the anaplastic lymphoma kinase (ALK) can be effectively targeted in advanced non-small cell lung cancer by ALK-TKI inhibitors including Crizotinib. However, the development of acquired resistance often limits the duration of these therapies. While several mechanisms of secondary resistance have been already identified, little is known about molecular determinants of primary resistance. In our brief report we investigated the tumor molecular profile of a patient who failed to respond to Crizotinib.
methodsFluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were run on tumor specimen as well as search and characterization of circulating tumor cells (CTCs) in the blood. Confirmation of clinical findings was achieved using a translational cell-line in vitro model.
resultsWe identified the amplification of MYC as a potential new mechanism of primary resistance to ALK inhibition. Human EML4-ALK rearranged cells infected with a lentiviral vector carrying full-length human MYC cDNA were treated in vitro with crizotinib and alectinib. Overexpression of MYC overexpression was associated with a reduced sensitivity to both ALK-inhibitors. MYC-overexpressing clones displayed also increased levels of both cyclin D and E and their growth was reduced by using Cdk4/6 inhibitors such as Palbociclib.
conclusionsWe postulate that the MYC gene may be implicated in the mechanism of primary resistance to ALK inhibitors. We also suggest potential MYC-directed inhibition strategies to overcome primary resistance in advanced ALK-rearranged NSCLC.
Identifiers
What OpenQuestion holds
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.