Faculty, Staff and Student Publications
CD70 Is a Therapeutic Target Upregulated in EMT-Associated Egfr Tyrosine Kinase Inhibitor Resistance
Publication Date
2-13-2023
Journal
Cancer Cell
Abstract
Effective therapeutic strategies are needed for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations that acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) mediated by epithelial-to-mesenchymal transition (EMT). We investigate cell surface proteins that could be targeted by antibody-based or adoptive cell therapy approaches and identify CD70 as being highly upregulated in EMT-associated resistance. Moreover, CD70 upregulation is an early event in the evolution of resistance and occurs in drug-tolerant persister cells (DTPCs). CD70 promotes cell survival and invasiveness, and stimulation of CD70 triggers signal transduction pathways known to be re-activated with acquired TKI resistance. Anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting chimeric antigen receptor (CAR) T cell and CAR NK cells show potent activity against EGFR TKI-resistant cells and DTPCs. These results identify CD70 as a therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits clinical investigation.
Keywords
Humans, Carcinoma, Non-Small-Cell Lung, CD27 Ligand, Cell Line, Tumor, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition, ErbB Receptors, Lung Neoplasms, Mutation, Tyrosine Kinase Inhibitors
DOI
10.1016/j.ccell.2023.01.007
PMID
36787696
PMCID
PMC10259078
PubMedCentral® Posted Date
2-13-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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