Use of liquid biopsy in monitoring therapeutic resistance in EGFR oncogene addicted NSCLC

Liquid biopsy has emerged as a minimally invasive alternative to tumor tissue analysis for the management of lung cancer patients, especially for epidermal growth factor receptor (EGFR) oncogene addicted tumor. In these patients, despite the clear benefits of tyrosine kinase inhibitors therapy, the development of acquired resistance and progressive disease is inevitable in most cases and liquid biopsy is important for molecular characterization at resistance and, being non-invasive, may be useful for disease monitoring. In this review, the authors will focus on the applications of liquid biopsy in EGFR-mutated non small cells lung cancer at diagnosis, during treatment and at progression, describing available data and possible future scenarios.

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Impact of clinical features on the efficacy of osimertinib treatment in epidermal growth factor receptor mutant non-small cell lung cancer patients with acquired resistance to tyrosine kinase inhibitors due to T790M mutation

Journal of Thoracic Disease ◽

10.21037/jtd.2019.08.117 ◽

2019 ◽

Vol 11 (S15) ◽

pp. S1847-S1851

Author(s):

Chong-Kin Liam ◽

Mau-Ern Poh ◽

Yong-Sheng Liam

Keyword(s):

Lung Cancer ◽

Kinase Inhibitors ◽

Acquired Resistance ◽

Growth Factor Receptor ◽

Small Cell ◽

Small Cell Lung ◽

T790m Mutation ◽

Lung Cancer Patients ◽

Epidermal Growth ◽

Receptor Mutant

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Mechanism of Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors and a Potential Treatment Strategy

Cells ◽

10.3390/cells7110212 ◽

2018 ◽

Vol 7 (11) ◽

pp. 212 ◽

Cited By ~ 49

Author(s):

Tatsuya Nagano ◽

Motoko Tachihara ◽

Yoshihiro Nishimura

Keyword(s):

Lung Cancer ◽

Growth Factor ◽

Kinase Inhibitors ◽

Acquired Resistance ◽

Growth Factor Receptor ◽

T790m Mutation ◽

Epidermal Growth ◽

Egfr Mutated ◽

Egfr Tki ◽

Egfr Tkis

Treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) improves the overall survival of patients with EGFR-mutated non-small-cell lung cancer (NSCLC). First-generation EGFR-TKIs (e.g., gefitinib and erlotinib) or second-generation EGFR-TKIs (e.g., afatinib and dacomitinib) are effective for the treatment of EGFR-mutated NSCLC, especially in patients with EGFR exon 19 deletions or an exon 21 L858R mutation. However, almost all cases experience disease recurrence after 1 to 2 years due to acquired resistance. The EGFR T790M mutation in exon 20 is the most frequent alteration associated with the development of acquired resistance. Osimertinib—a third-generation EGFR-TKI—targets the T790M mutation and has demonstrated high efficacy against EGFR-mutated lung cancer. However, the development of acquired resistance to third-generation EGFR-TKI, involving the cysteine residue at codon 797 mutation, has been observed. Other mechanisms of acquired resistance include the activation of alternative pathways or downstream targets and histological transformation (i.e., epithelial–mesenchymal transition or conversion to small-cell lung cancer). Furthermore, the development of primary resistance through overexpression of the hepatocyte growth factor and suppression of Bcl-2-like protein 11 expression may lead to problems. In this report, we review these mechanisms and discuss therapeutic strategies to overcome resistance to EGFR-TKIs.

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