Tumor clonality and resistance mechanisms in EGFR mutation-positive non-small-cell lung cancer : implications for therapeutic sequencing
While the development of EGFR-targeted tyrosine kinase inhibitors (TKIs) has revolutionized treatment of EGFR mutation-positive non-small-cell lung cancer, acquired resistance to therapy is inevitable, reflecting tumor evolution. Recent studies show that EGFR mutation-positive non-small-cell lung cancer is highly heterogeneous at the cellular level, facilitating clonal expansion of resistant tumors via multiple molecular mechanisms. Here, we review the mechanistic differences between first-, second- and third-generation EGFR-targeted TKIs and speculate how these features could explain differences in clinical activity between these agents from a clonal evolution perspective. We hypothesize that the molecular dissection of tumor resistance mechanisms will facilitate optimal sequential use of EGFR TKIs in individual patients, thus maximizing the duration of chemotherapy-free treatment and survival benefit.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Future oncology (London, England) - 15(2019), 6 vom: 01. Feb., Seite 637-652 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kohsaka, Shinji [VerfasserIn] |
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| Links: |
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| Themen: |
Acquired resistance |
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| Anmerkungen: |
Date Completed 12.08.2019 Date Revised 12.08.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.2217/fon-2018-0736 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM290373824 |
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| 520 | |a While the development of EGFR-targeted tyrosine kinase inhibitors (TKIs) has revolutionized treatment of EGFR mutation-positive non-small-cell lung cancer, acquired resistance to therapy is inevitable, reflecting tumor evolution. Recent studies show that EGFR mutation-positive non-small-cell lung cancer is highly heterogeneous at the cellular level, facilitating clonal expansion of resistant tumors via multiple molecular mechanisms. Here, we review the mechanistic differences between first-, second- and third-generation EGFR-targeted TKIs and speculate how these features could explain differences in clinical activity between these agents from a clonal evolution perspective. We hypothesize that the molecular dissection of tumor resistance mechanisms will facilitate optimal sequential use of EGFR TKIs in individual patients, thus maximizing the duration of chemotherapy-free treatment and survival benefit | ||
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| 700 | 1 | |a Maemondo, Makoto |e verfasserin |4 aut | |
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