Related Experiment Video
Updated: Apr 30, 2026
Author Spotlight: Evaluating Therapeutic Strategies to Enhance Liver Regeneration
Published on: May 24, 2024
Everolimus prolonged survival in transgenic mice with EGFR-driven lung tumors
Masayuki Yasugi1, Nagio Takigawa2, Nobuaki Ochi3
1Department of Hematology, Oncology, and Respiratory Medicine, Okayama, University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Abstract:
Everolimus is an orally administered mTOR inhibitor. The effect, and mechanism of action, of everolimus on lung cancers with an epidermal growth factor receptor (EGFR) mutation remain unclear. Four gefitinib-sensitive and -resistant cell lines were used in the present work. Growth inhibition was determined using the MTT assay. Transgenic mice carrying the EGFR L858R mutation were treated with everolimus (10 mg/kg/day), or vehicle alone, from 5 to 20 weeks of age, and were then sacrificed. To evaluate the efficacy of everolimus in prolonging survival, everolimus (10 mg/kg/day) or vehicle was administered from 5 weeks of age. The four cell lines were similarly sensitive to everolimus. Expression of phosphorylated (p) mTOR and pS6 were suppressed upon treatment with everolimus in vitro, whereas the pAKT level increased. The numbers of lung tumors with a long axis exceeding 1mm in the everolimus-treated and control groups were 1.9 ± 0.9 and 9.4 ± 3.2 (t-test, p<0.001), respectively. pS6 was suppressed during eve r olimus treatment. Although apoptosis and autophagy were not induced in everolimus-treated EGFR transgenic mice, angiogenesis was suppressed. The median survival time in the everolimus-treated group (58.0 weeks) was significantly longer than that in the control group (31.2 weeks) (logrank test, p<0.001). These findings suggest that everolimus had an indirect effect on tumor formation by inhibiting angiogenesis and might be effective to treat lung tumors induced by an activating EGFR gene mutation.
Insights
Everolimus, an mTOR inhibitor, effectively reduced lung tumors in mice with EGFR mutations by inhibiting angiogenesis, significantly improving survival rates. This suggests its potential for treating such lung cancers.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Lung cancer remains a leading cause of cancer-related deaths worldwide.
- Epidermal growth factor receptor (EGFR) mutations are common drivers in certain lung cancers.
- The therapeutic role of mTOR inhibitors like everolimus in EGFR-mutated lung cancer is not fully understood.
Purpose of the Study:
- To investigate the effect and mechanism of action of everolimus on lung cancers with EGFR mutations.
- To evaluate everolimus's efficacy in inhibiting tumor growth and prolonging survival in a preclinical model.
Main Methods:
- Utilized gefitinib-sensitive and -resistant lung cancer cell lines for in vitro studies.
- Assessed cell growth inhibition using the MTT assay.
- Administered everolimus to transgenic mice with EGFR L858R mutations and analyzed tumor burden, angiogenesis, apoptosis, autophagy, and survival.
Main Results:
- Everolimus demonstrated sensitivity across tested EGFR-mutated lung cancer cell lines.
- In vitro, everolimus suppressed phosphorylated mTOR and S6, with a concurrent increase in phosphorylated AKT.
- In vivo, everolimus significantly reduced lung tumor numbers and suppressed angiogenesis without inducing apoptosis or autophagy, leading to a median survival of 58.0 weeks compared to 31.2 weeks in controls.
Conclusions:
- Everolimus exhibits antitumor activity in EGFR-mutated lung cancer models.
- The mechanism involves inhibition of angiogenesis, suggesting an indirect effect on tumor formation.
- Everolimus may be a promising therapeutic option for lung tumors driven by activating EGFR mutations.
