MDM2 drives resistance to Osimertinib by contextually disrupting FBW7-mediated destruction of MCL-1 protein in EGFR mutant NSCLC
Overexpression of MDM2 is a novel resistant mechanism to Osimertinib in EGFR mutant NSCLC. MDM2 utilizes its E3 ligase activity to provoke FBW7 destruction and sequentially leads to MCL-1 stabilization. Cancer cells with aberrant MDM2 state are refractory to apoptosis induction and elicit a resistant phenotype to Osimertinib. Therefore, targeting MDM2 would be a feasible approach to overcome resistance to Osimertinib in EGFR mutant NSCLC.
Authors
- Lingyun Wei
- Liang Cao (ORCID: https://orcid.org/0000-0001-7293-8338)
- Jiaxin Liu (ORCID: https://orcid.org/0009-0009-1076-9124)
- Tangfeng Lv (ORCID: https://orcid.org/0000-0001-7224-8468)
- Qing Miao (ORCID: https://orcid.org/0000-0002-3125-1238)
- Yong Song (ORCID: https://orcid.org/0000-0002-0890-6662)
- Mingxiang Ye
- Jie Yin (ORCID: https://orcid.org/0000-0003-2611-0112)
- Dong Wang (ORCID: https://orcid.org/0000-0003-3489-915X)
- Wei Liu (ORCID: https://orcid.org/0000-0002-1727-6738)
- Hongbing Liu (ORCID: https://orcid.org/0000-0002-3017-9668)
- Peilin Chen (ORCID: https://orcid.org/0000-0003-4154-0487)
- Sutong Zhan
Institutions
- Nanjing General Hospital of Nanjing Military Command (CN)
- Nanjing Drum Tower Hospital (CN)
- Nanjing Medical University (CN)
- Nanjing University (CN)
- Air Force Medical University (CN)
Publication Details
- Journal
- Journal of Experimental & Clinical Cancer Research
- Published
- 2024-11-15
- DOI
- https://doi.org/10.1186/s13046-024-03220-7
- Citations
- 6
- Primary Topic
- Lung Cancer Treatments and Mutations
- Type
- article
- Field-Weighted Citation Impact
- 2.51
Funders
- University of Missouri
- University of Texas Southwestern Medical Center
- Shaanxi Administration of Traditional Chinese Medicine
- National Natural Science Foundation of China
- Natural Science Foundation of Shandong Province
- Novartis Institutes for BioMedical Research