ArticleScientific reports2019
Mechanisms of suppression of cell growth by dual inhibition of ALK and MEK in ALK-positive non-small cell lung cancer.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Safety and activity of alectinib plus bevacizumab in patients with advanced ALK-rearranged non-small-cell lung cancer: a phase I/II study.ESMO open · 2022Trial
- ALK rearrangements and resistance mutations in non-small cell lung cancer: molecular mechanisms and therapeutic implications.Cancer chemotherapy and pharmacology · 2026Review
- Resistance to EGFR Inhibitors in NSCLC: Mechanistic Insights and Emerging Therapies.International journal of molecular sciences · 2026Review
- Therapy-induced cholesterol biosynthesis drives lung cancer dormancy and drug resistance.The Journal of clinical investigation · 2026Article
- Article
- New advances in understanding the mechanisms and treatment challenges of ALK-targeted therapy resistance in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- Article
- Targeting MEK in non-small cell lung cancer.Current problems in cancer · 2024Review
- Mechanisms of synergistic suppression of ALK-positive lung cancer cell growth by the combination of ALK and SHP2 inhibitors.Scientific reports · 2023Article
- Molecular pathways, resistance mechanisms and targeted interventions in non-small-cell lung cancer.Molecular biomedicine · 2022Review
- Synergistic Drug Combinations Prevent Resistance in ALK+ Anaplastic Large Cell Lymphoma.Cancers · 2021Article
- High Antiproliferative Activity of Hydroxythiopyridones over Hydroxypyridones and Their Organoruthenium Complexes.Biomedicines · 2021Article
- Resistance to anaplastic lymphoma kinase inhibitors: knowing the enemy is half the battle won.Translational lung cancer research · 2020Review
- [Advances in Drug Resistance Mechanisms and Prognostic Markers of Targeted Therapy in ALK-positive Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2020Review
- Development of an ALK-positive Non-Small-Cell Lung Cancer in Vitro Tumor 3D Culture Model for Therapeutic Screening.The journal of histochemistry and cytochemistry : official journal of the Histochemistry SocietyArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anaplastic lymphoma kinase (ALK) rearrangement, a key oncogenic driver in a small subset of non-small cell lung cancers, confers sensitivity to ALK tyrosine kinase inhibitors (TKIs). Crizotinib, a first generation ALK-TKI, has superiority to standard chemotherapy with longer progression-free survival and higher objective response rate. However, clinical benefit is limited by development of resistance, typically within a year of therapy. In this study the combined effect of crizotinib and the MEK inhibitor selumetinib was investigated in both crizotinib naïve (H3122) and crizotinib resistant (CR-H3122) ALK-positive lung cancer cells. Results showed that combination treatment potently inhibited the growth of both H3122 and CR-H3122 cells, resulting from increased apoptosis and decreased cell proliferation as a consequence of suppressed downstream RAS/MAPK signalling. The drug combination also elicited a greater than 3-fold increase in Bim, a mediator of apoptosis, and p27, a cyclin dependent kinase inhibitor compared to crizotinib alone. The results support the hypothesis that combining MEK inhibitors with ALK inhibitor can overcome ALK inhibitor resistance, and identifies Bim, PARP and CDK1 as druggable targets for possible triple drug therapy.
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Registered trials
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