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Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer

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Abstract

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) represents a paradigm shift in the treatment of non-small cell lung cancer (NSCLC) patients and has been the first-line therapy in clinical practice. While erlotinib, gefitinib and afatinib have achieved superior efficacy in terms of progression-free survival and overall survival compared with conventional chemotherapy in NSCLC patients, most people inevitably develop acquired resistance to them, which presents another challenge in the treatment of NSCLC. The mechanisms of acquired resistance can be classified as three types: target gene mutation, bypass signaling pathway activation and histological transformation. And the most common mechanism is T790M which accounts for approximately 50% of all subtypes. Many strategies have been explored to overcome the acquired resistance to EGFR TKI. Continuation of EGFR TKI beyond progressive disease is confined to patients in asymptomatic stage when the EGFR addiction is still preserved in some subclones. While the combination of EGFR TKI and chemotherapy or other targeted agents has improved the survival benefit in EGFR TKI resistant patients, there are controversies within them. The next-generation EGFR TKI and immunotherapy represent two novel directions for overcoming acquired resistance and have achieved promising efficacy. Liquid biopsy provides surveillance of the EGFR mutation by disclosing the entire genetic landscape but tissue biopsy is still indispensable because of the considerable rate of false-negative plasma.

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Abbreviations

EGFR TKI:

Epidermal growth factor receptor tyrosine kinase inhibitor

NSCLC:

Non-small cell lung cancer

PFS:

Progression-free survival

OS:

Overall survival

PD:

Progressive disease

RR:

Response rate

ATP:

Adenosine triphosphate

ORR:

Objective response rate

CNS:

Central nervous system

AE:

Adverse event

WT:

Wild type

ILD:

Interstitial lung disease

PD-1:

Programmed death 1

PD-L1:

Programmed death ligand 1

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Acknowledgements

This study was funded by Talent Funding Program of Zhongshan Hospital of Fudan University.

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  1. J. Gao and H.-R. Li contributed equally to this work.

Authors and Affiliations

  1. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China

    J. Gao, H.-R. Li, C. Jin, J.-H. Jiang & J.-Y. Ding

  2. Department of Thoracic Surgery, Xuhui District Center Hospital of Shanghai, Shanghai, 200031, China

    C. Jin

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  1. J. Gao
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  2. H.-R. Li
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  3. C. Jin
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  4. J.-H. Jiang
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Correspondence to J.-Y. Ding.

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Gao, J., Li, HR., Jin, C. et al. Strategies to overcome acquired resistance to EGFR TKI in the treatment of non-small cell lung cancer. Clin Transl Oncol 21, 1287–1301 (2019). https://doi.org/10.1007/s12094-019-02075-1

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  • DOI: https://doi.org/10.1007/s12094-019-02075-1

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