ArticleScientific reports2018
Structure and energy based quantitative missense variant effect analysis provides insights into drug resistance mechanisms of anaplastic lymphoma kinase mutations.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Reading between the Chains: Surface Mapping and Druggable Pockets on the Biological Assemblies of DENV-2's Protein E.ACS omega · 2026Article
- A comprehensive functional atlas of ALK kinase domain variants reveals resistance landscape to ALK inhibitors.Genome biology · 2026Article
- Resistance mutations and the blood-brain barrier: Key challenges in targeted treatment of brain metastatic non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2025Review
- Unraveling Extremely DamagingJournal of personalized medicine · 2023Article
- A computational examination of the therapeutic advantages of fourth-generation ALK inhibitors TPX-0131 and repotrectinib over third-generation lorlatinib for NSCLC with ALK F1174C/L/V mutations.Frontiers in molecular biosciences · 2023Article
- Targeting ALK Rearrangements in NSCLC: Current State of the Art.Frontiers in oncology · 2022Review
- NGS-based liquid biopsy profiling identifies mechanisms of resistance to ALK inhibitors: a step toward personalized NSCLC treatment.Molecular oncology · 2021Article
- Head to head evaluation of second generation ALK inhibitors brigatinib and alectinib as first-line treatment for ALK+ NSCLC using anOncotarget · 2021Article
- Deciphering the Mechanism of Gilteritinib Overcoming Lorlatinib Resistance to the Double Mutant I1171N/F1174I in Anaplastic Lymphoma Kinase.Frontiers in cell and developmental biology · 2021Article
- Next-generation sequencing to dynamically detect mechanisms of resistance toTranslational lung cancer research · 2020Article
- Insight into the structural stability of wild-type and histidine mutants in Pin1 by experimental and computational methods.Scientific reports · 2019Article
- SNP2SIM: a modular workflow for standardizing molecular simulation and functional analysis of protein variants.BMC bioinformatics · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Anaplastic lymphoma kinase (ALK) is considered as a validated molecular target in multiple malignancies, such as non-small cell lung cancer (NSCLC). However, the effectiveness of molecularly targeted therapies using ALK inhibitors is almost universally limited by drug resistance. Drug resistance to molecularly targeted therapies has now become a major obstacle to effective cancer treatment and personalized medicine. It is of particular importance to provide an improved understanding on the mechanisms of resistance of ALK inhibitors, thus rational new therapeutic strategies can be developed to combat resistance. We used state-of-the-art computational approaches to systematically explore the mutational effects of ALK mutations on drug resistance properties. We found the activation of ALK was increased by substitution with destabilizing mutations, creating the capacity to confer drug resistance to inhibitors. In addition, results implied that evolutionary constraints might affect the drug resistance properties. Moreover, an extensive profile of drugs against ALK mutations was constructed to give better understanding of the mechanism of drug resistance based on structural transitions and energetic variation. Our work hopes to provide an up-to-date mechanistic framework for understanding the mechanisms of drug resistance induced by ALK mutations, thus tailor treatment decisions after the emergence of resistance in ALK-dependent diseases.
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Registered trials
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