ArticleMolecular oncology2021
NGS-based liquid biopsy profiling identifies mechanisms of resistance to ALK inhibitors: a step toward personalized NSCLC treatment.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Current status and challenges of immunotherapy in ALK rearranged NSCLC.Frontiers in oncology · 2022Pooled it
- Identification of candidate variants in plasma associated with early versus late disease progression under anti-PD-1 therapy in metastatic NSCLC.Translational lung cancer research · 2026Article
- Liquid biopsy in solid tumours: expert opinion paper of the European society of pathology.Virchows Archiv : an international journal of pathology · 2026Review
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Review
- Comprehensive Liquid Biopsy Approaches for the Clinical Management of Lung Cancer Using Multiple Biological Matrices.International journal of molecular sciences · 2025Review
- Demonstrating the clinical utility of genomic profiling using cerebrospinal fluid to inform management of central nervous system tumors - a meta analysis of the literature.The journal of liquid biopsy · 2025Review
- Circulating tumor DNA in ALK-positive anaplastic large cell lymphoma: a proof-of-concept study.NPJ precision oncology · 2025Article
- The latest advances in liquid biopsy for lung cancer-a narrative review.Translational lung cancer research · 2024Review
- Integrated approach to generate artificial samples with low tumor fraction for somatic variant calling benchmarking.BMC bioinformatics · 2024Article
- Article
- Unraveling the Potential of ALK-Targeted Therapies in Non-Small Cell Lung Cancer: Comprehensive Insights and Future Directions.Biomedicines · 2024Review
- Management strategies for intracranial progression in ALK-positive non-small cell lung cancer: a real-world cohort study.Journal of neuro-oncology · 2023Article
- Prognostic Value of Circulating Tumor DNA (ctDNA) in Oncogene-Driven NSCLC: Current Knowledge and Future Perspectives.Cancers · 2022Review
- Review
- Morphologic-Molecular Transformation of Oncogene Addicted Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Review
- Circulating tumor DNA detection in MRD assessment and diagnosis and treatment of non-small cell lung cancer.Frontiers in oncology · 2022Review
- Clinical Applications of Circulating Tumour Cells and Circulating Tumour DNA in Non-Small Cell Lung Cancer-An Update.Frontiers in oncology · 2022Review
- Case Report: A Pregnant Woman Diagnosed as ALK-Rearrangement Lung Large Cell Neuroendocrine Cancer With Brain Metastasis.Frontiers in oncology · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite impressive and durable responses, nonsmall cell lung cancer (NSCLC) patients treated with anaplastic lymphoma kinase (ALK) inhibitors (ALK-Is) ultimately progress due to development of resistance. Here, we have evaluated the clinical utility of circulating tumor DNA (ctDNA) profiling by next-generation sequencing (NGS) upon disease progression. We collected 26 plasma and two cerebrospinal fluid samples from 24 advanced ALK-positive NSCLC patients at disease progression to an ALK-I. These samples were analyzed by NGS and digital PCR. A tool to retrieve variants at the ALK locus was developed (VALK tool). We identified at least one resistance mutation in the ALK locus in ten (38.5%) plasma samples; the G1269A and G1202R mutations were the most prevalent among patients progressing to first- and second-generation ALK-Is, respectively. Overall, 61 somatic mutations were detected in 14 genes: TP53, ALK, PIK3CA, SMAD4, MAP2K1 (MEK1), FGFR2, FGFR3, BRAF, EGFR, IDH2, MYC, MET, CCND3, and CCND1. Specifically, a deletion in exon 19 in EGFR, a non-V600 BRAF mutation (G466V), and the F129L mutation in MAP2K1 were identified in four patients who showed no objective survival benefit from ALK-Is. Potential ALK-I-resistance mutations were also found in PIK3CA and IDH2. Finally, a c-MYC gain, along with a loss of CCND1 and FGFR3, was detected in a patient progressing on a first-line treatment with crizotinib. We conclude that NGS analysis of liquid biopsies upon disease progression identified different putative ALK-I-resistance mutations in most cases and could be a valuable approach for therapy decision making.
Indexed as
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.