CD70 is a therapeutic target upregulated in EMT-associated EGFR tyrosine kinase inhibitor resistance
Copyright © 2023. Published by Elsevier Inc..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Cancer cell - 41(2023), 2 vom: 13. Feb., Seite 340-355.e6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nilsson, Monique B [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.02.2023 Date Revised 14.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.ccell.2023.01.007 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM352942908 |
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| 100 | 1 | |a Nilsson, Monique B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a CD70 is a therapeutic target upregulated in EMT-associated EGFR tyrosine kinase inhibitor resistance |
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| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023. Published by Elsevier Inc. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Yang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Heeke, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Sonia A |e verfasserin |4 aut | |
| 700 | 1 | |a Poteete, Alissa |e verfasserin |4 aut | |
| 700 | 1 | |a Udagawa, Hibiki |e verfasserin |4 aut | |
| 700 | 1 | |a Elamin, Yasir Y |e verfasserin |4 aut | |
| 700 | 1 | |a Moran, Cesar A |e verfasserin |4 aut | |
| 700 | 1 | |a Kashima, Yukie |e verfasserin |4 aut | |
| 700 | 1 | |a Arumugam, Thiruvengadam |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xiaoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Xiaoyang |e verfasserin |4 aut | |
| 700 | 1 | |a Diao, Lixia |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Minying |e verfasserin |4 aut | |
| 700 | 1 | |a Robichaux, Jacqulyne P |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Chunhua |e verfasserin |4 aut | |
| 700 | 1 | |a Pfeil, Allyson N |e verfasserin |4 aut | |
| 700 | 1 | |a Tran, Hai |e verfasserin |4 aut | |
| 700 | 1 | |a Gibbons, Don L |e verfasserin |4 aut | |
| 700 | 1 | |a Bock, Jason |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Minna, John D |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Susumu S |e verfasserin |4 aut | |
| 700 | 1 | |a Le, Xiuning |e verfasserin |4 aut | |
| 700 | 1 | |a Heymach, John V |e verfasserin |4 aut | |
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