ArticleNPJ precision oncology2023
Adaptive resistance to lorlatinib via EGFR signaling in ALK-rearranged lung cancer.
Article in NPJ precision oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 28 citations in OpenAlex.
- Combined therapy with ALK inhibitors and a novel EGFR-targeting antibody‒drug conjugate as a strategy for ALK-rearranged non-small cell lung cancers.Oncogenesis · 2026Article
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Review
- AcquiredFrontiers in oncology · 2026Article
- Advances in Targeting Growth Factor Signalling in Neuroblastoma and Overcoming Drug Resistance.Cells · 2025Review
- BRAF mutations and targeted therapy in unclassified pericytic tumors: insights from genetic analysis and clinical response.BMC cancer · 2025Article
- Anti-EGFR therapy can overcome acquired resistance to the third-generation ALK-tyrosine kinase inhibitor lorlatinib mediated by activation of EGFR.Acta pharmacologica Sinica · 2025Article
- Lorlatinib in ALK-positive non-small cell lung cancer: final survival data that reshape the therapeutic landscape.Translational lung cancer research · 2025Article
- Utility of serum CYFRA 21-1 as a prognostic biomarker in ALK-positive non-small cell lung cancer treated with ALK-TKIs: a retrospective cohort study.Translational lung cancer research · 2025Article
- Article
- Targeting ERBB3 and AKT to overcome adaptive resistance in EML4-ALK-driven non-small cell lung cancer.Cell death & disease · 2024Article
- Targeting ErbB and tankyrase1/2 prevent the emergence of drug-tolerant persister cells in ALK-positive lung cancer.NPJ precision oncology · 2024Article
- Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance.Nature communications · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- Transforming tumoroids derived from ALK-positive pulmonary adenocarcinoma to squamous cell carcinoma in vivo.Human cell · 2024Article
- HER3 overexpression: a predictive marker for poor prognosis in advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors.Translational lung cancer research · 2024Article
- A single cell RNAseq benchmark experiment embedding "controlled" cancer heterogeneity.Scientific data · 2024Article
- From Development to Place in Therapy of Lorlatinib for the Treatment of ALK and ROS1 Rearranged Non-Small Cell Lung Cancer (NSCLC).Diagnostics (Basel, Switzerland) · 2023Review
- MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.JCI insight · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 6 institutions in 1 country.
Funding
Abstract
Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors rarely elicit complete responses in patients with advanced ALK-rearranged non-small cell lung cancer (NSCLC), as a small population of tumor cells survives due to adaptive resistance. Therefore, we focused on the mechanisms underlying adaptive resistance to lorlatinib and therapeutic strategies required to overcome them. We found that epidermal growth factor receptor (EGFR) signaling was involved in the adaptive resistance to lorlatinib in ALK-rearranged NSCLC, activation of which was induced by heparin-binding EGF-like growth factor production via c-Jun activation. EGFR inhibition halted ALK-rearranged lung cancer cell proliferation by enhancing ALK inhibition-induced apoptosis via suppression of Bcl-xL. Xenograft models showed that the combination of EGFR inhibitor and lorlatinib considerably suppressed tumor regrowth following cessation of these treatments. This study provides new insights regarding tumor evolution due to EGFR signaling after lorlatinib treatment and the development of combined therapeutic strategies for ALK-rearranged lung cancer.
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.