ArticleMolecular cancer2022
Costunolide is a dual inhibitor of MEK1 and AKT1/2 that overcomes osimertinib resistance in lung cancer.
Article in Molecular cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- A novel regulator in cancer initiation and progression: long noncoding RNA SHNG9.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Pooled it
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- Cryptotanshinone Directly Targets MEK1 to Inhibit Migration and Invasion of Breast Cancer Cells Through Down-Regulating ERK/EMT Axis.Phytotherapy research : PTR · 2026Article
- Integrating network pharmacology, molecular dynamics, and in vitro assays to unveil the mechanism of costunolide against gastric cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Identifying the potential anti-lung cancer targets of Baicalein using a network pharmacology approach.Scientific reports · 2026Article
- Traditional Chinese medicine reprograms the tumor microenvironment to overcome EGFR-TKI resistance: mechanisms and therapeutic perspectives.Frontiers in pharmacology · 2026Review
- Potential Anti-Cancer Drug 6RK73 Suppresses Ovarian Cancer Growth by Inactivating the AKT1/Sp1 Induced c-Myc Signaling Pathway.Journal of Cancer · 2026Article
- Natural compounds for non-small cell lung cancer treatment: focus on the EGFR signaling pathway.Frontiers in pharmacology · 2026Review
- Study on the mechanism of costunolide inhibiting triple-negative breast cancer by EGFR ubiquitination and degradation to suppress the ERK/AKT signaling pathway.Journal of molecular histology · 2025Article
- Hypoxia-inducible APCDD1L-AS1 promotes osimertinib resistance by stabilising DLST to drive tricarboxylic acid cycle in lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Costunolide normalizes neuroinflammation and improves neurogenesis deficits in a mouse model of depression through inhibiting microglial Akt/mTOR/NF-κB pathway.Acta pharmacologica Sinica · 2025Article
- Isorhamnetin inhibits cholangiocarcinoma proliferation and metastasis via PI3K/AKT signaling pathway.Discover oncology · 2025Article
- Combining network pharmacology and molecular docking to explore the pharmacological mechanism of Codonopsis Radix.-Hedysarum Multijugum Maxim.-Atractylodes Macrocephala Koidz. in treating lung cancer.BMC complementary medicine and therapies · 2025Article
- Review
- Research advances in natural sesquiterpene lactones: overcoming cancer drug resistance through modulation of key signaling pathways.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- 3-Oxo-11αH-germacra-1(10) E,4Z-dien-12,6α-olide, a sesquiterpene from Artemisia sieversiana, attenuates lipopolysaccharide-induced inflammation via NF-κB/MAPK pathways and oxidative stress via ROS pathway in RAW264.7 cells.Journal of natural medicines · 2025Article
- Toxicity mechanism analysis of cGAS-STING-TBK1 signaling pathway small molecule modulator based on network toxicology and molecular docking strategy: quinacrine acetate as an example.Frontiers in chemistry · 2025Article
- Assembly factor for spindle microtubules (Frontiers in genetics · 2025Article
- Cytoglobin suppresses oxidative damage and compensatory proliferation via inhibiting AKT/ERK1/2/CyclinD1 axis in hepatocellular carcinoma.American journal of cancer research · 2025Article
- Abnormally Activated MNX1 Promotes Tumor Growth and Osimertinib Resistance and Predicts Survival in EGFR-Mutant Lung Adenocarcinoma.Drug design, development and therapy · 2025Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EGFR-TKI targeted therapy is one of the most effective treatments for lung cancer patients harboring EGFR activating mutations. However, inhibition response is easily attenuated by drug resistance, which is mainly due to bypass activation or downstream activation. Herein, we established osimertinib-resistant cells by stepwise dose-escalation in vitro and an osimertinib-resistant patient-derived xenograft model through persistent treatment in vivo. Phosphorylated proteomics identified that MEK1 and AKT1/2 were abnormally activated in resistant cells compared with parental cells. Likewise, EGFR inhibition by osimertinib induced activation of MEK1 and AKT1/2, which weakened osimertinib sensitivity in NSCLC cells. Consequently, this study aimed to identify a novel inhibitor which could suppress resistant cell growth by dual targeting of MEK1 and AKT1/2. Based on computational screening, we identified that costunolide could interact with MEK1 and AKT1/2. Further exploration using in vitro kinase assays validated that costunolide inhibited the kinase activity of MEK1 and AKT1/2, which restrained downstream ERK-RSK2 and GSK3β signal transduction and significantly induced cell apoptosis. Remarkably, the combination of osimertinib and costunolide showed synergistic or additive inhibitory effects on tumor growth in osimertinib-resistant cell lines and PDX model. Hence, this study highlights a potential therapeutic strategy for osimertinib-resistant patients through targeting of MEK1 and AKT1/2 by costunolide.
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