ArticleCell reports. Medicine2024
A bispecific antibody targeting EGFR and AXL delays resistance to osimertinib.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Window-of-Opportunity Study Utilizing Preoperative Cetuximab in Patients with Head and Neck Cancer.Cancer research communications · 2026Article
- Comprehensive analysis of antibody-drug conjugate (ADC) targets in adenoid cystic carcinoma: examining antigen expression in relation to clinicopathological features, prognosis, and initial therapeutic outcomes.Translational oncology · 2026Article
- Bidirectional coupling among EMT, AXL-RB1 signaling and lineage switch drives resistance to osimertinib and worse clinical outcomes in NSCLC.bioRxiv : the preprint server for biology · 2026Article
- Non-enzymatic function of QSOX2 directly regulates the JUNB-ITGB4 axis and enhanced resistance to osimertinib in EGFR-mutation lung adenocarcinoma.Cell death discovery · 2026Article
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- [Role of Receptor Tyrosine Kinase AXL in Cancer Targeted Therapy Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- The methylation pattern of osimertinib resistance: prospects for diagnosis and treatment of NSCLC.Frontiers in oncology · 2026Review
- In vitro synergistic effect of AXL, FAK and ErbB receptors inhibitors for head and neck cancer.Biology direct · 2025Article
- Strategies Beyond 3rd EGFR-TKI Acquired Resistance: Opportunities and Challenges.Cancer medicine · 2025Review
- Recent advances in TAM mechanisms in lung diseases.Journal of translational medicine · 2025Review
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- Review
- Osimertinib acquired resistance among patients with EGFR-mutated NSCLC: from molecular mechanisms to clinical therapeutic strategies.Cancer drug resistance (Alhambra, Calif.) · 2025Review
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Authors and funding
17 authors.
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Abstract
Activating EGFR (epidermal growth factor receptor) mutations can be inhibited by specific tyrosine kinase inhibitors (TKIs), which have changed the landscape of lung cancer therapy. However, due to secondary mutations and bypass receptors, such as AXL (AXL receptor tyrosine kinase), drug resistance eventually emerges in most patients treated with the first-, second-, or third-generation TKIs (e.g., osimertinib). To inhibit AXL and resistance to osimertinib, we compare two anti-AXL drugs, an antibody (mAb654) and a TKI (bemcentinib). While no pair of osimertinib and an anti-AXL drug is able to prevent relapses, triplets combining osimertinib, cetuximab (an anti-EGFR antibody), and either anti-AXL drug are initially effective. However, longer monitoring uncovers superiority of the mAb654-containing triplet, possibly due to induction of receptor endocytosis, activation of immune mechanisms, or disabling intrinsic mutators. Hence, we constructed a bispecific antibody that engages both AXL and EGFR. When combined with osimertinib, the bispecific antibody consistently inhibits tumor relapses, which warrants clinical trials.
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