Basic Understandings of EGFR-mutated Lung Cancer and Its Clinical Applications

AbstractExosomes are major contributors in cell to cell communication due to their ability to transfer biological material such as protein, RNA, DNA, and miRNA. Additionally, they play a role in tumor initiation, promotion, and progression, and recently, they have emerged as a potential source of information on tumor detection and may be useful as diagnostic, prognostic, and predictive tools. This review focuses on exosomes from lung cancer with a focus on EGFR mutations. Here, we outline the role of exosomes and their functional effect in carcinogenesis, tumor progression, and metastasis. Finally, we discuss the possibility of exosomes as novel biomarkers in early detection, diagnosis, assessment of prognosis, and prediction of therapeutic response in EGFR-mutated lung cancer.

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Acquired Resistance to Osimertinib Plus Savolitinib Is Mediated by MET-D1228 and MET-Y1230 Mutations in EGFR-Mutated MET-Amplified Lung Cancer

JTO Clinical and Research Reports ◽

10.1016/j.jtocrr.2020.100071 ◽

2020 ◽

Vol 1 (4) ◽

pp. 100071

Author(s):

Andrew J. Piper-Vallillo ◽

Brian T. Halbert ◽

Deepa Rangachari ◽

Susumu S. Kobayashi ◽

Daniel B. Costa

Keyword(s):

Lung Cancer ◽

Acquired Resistance ◽

Egfr Mutated

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A multicenter cohort study of osimertinib compared with afatinib as first-line treatment for EGFR-mutated non-small-cell lung cancer from practical dataset: CJLSG1903

ESMO Open ◽

10.1016/j.esmoop.2021.100115 ◽

2021 ◽

Vol 6 (3) ◽

pp. 100115

Author(s):

K. Ito ◽

M. Morise ◽

K. Wakuda ◽

O. Hataji ◽

T. Shimokawaji ◽

...

Keyword(s):

Lung Cancer ◽

Cohort Study ◽

Small Cell ◽

Line Treatment ◽

Small Cell Lung ◽

First Line ◽

Multicenter Cohort Study ◽

Multicenter Cohort ◽

Egfr Mutated ◽

First Line Treatment

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Drug Tolerance to EGFR Tyrosine Kinase Inhibitors in Lung Cancers with EGFR Mutations

Cells ◽

10.3390/cells10071590 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1590

Author(s):

Kenichi Suda ◽

Tetsuya Mitsudomi

Keyword(s):

Lung Cancer ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Molecular Mechanisms ◽

Kinase Inhibitors ◽

Drug Tolerance ◽

Lung Cancers ◽

Egfr Tyrosine Kinase ◽

Egfr Tyrosine Kinase Inhibitors ◽

Egfr Mutated

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) serve as the standard of care for the first-line treatment of patients with lung cancers with EGFR-activating mutations. However, the acquisition of resistance to EGFR TKIs is almost inevitable, with extremely rare exceptions, and drug-tolerant cells (DTCs) that demonstrate reversible drug insensitivity and that survive the early phase of TKI exposure are hypothesized to be an important source of cancer cells that eventually acquire irreversible resistance. Numerous studies on the molecular mechanisms of drug tolerance of EGFR-mutated lung cancers employ lung cancer cell lines as models. Here, we reviewed these studies to generally describe the features, potential origins, and candidate molecular mechanisms of DTCs. The rapid development of an optimal treatment for EGFR-mutated lung cancer will require a better understanding of the underlying molecular mechanisms of the drug insensitivity of DTCs.

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A phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected non-small-cell lung cancer with EGFR mutation (West Japan Oncology Group 11719L/ADJUST study)

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920987647 ◽

2021 ◽

Vol 13 ◽

pp. 175883592098764

Author(s):

Ryota Shibaki ◽

Hiroaki Akamatsu ◽

Terufumi Kato ◽

Kazumi Nishino ◽

Morihito Okada ◽

...

Keyword(s):

Lung Cancer ◽

Adjuvant Therapy ◽

Egfr Mutation ◽

Phase Ii Study ◽

Small Cell ◽

Small Cell Lung ◽

Resected Nsclc ◽

Egfr Mutated ◽

Doublet Chemotherapy ◽

Platinum Doublet

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is a standard treatment in EGFR-mutated advanced non-small-cell lung cancer (NSCLC); however, previous data have suggested that EGFR-TKI has limited potential as adjuvant therapy. On the contrary, based on subset analysis with the immune checkpoint inhibitor (ICI) plus platinum-doublet chemotherapy in advanced NSCLC with EGFR mutation, we hypothesized that this combination was worth testing as adjuvant therapy in patients with EGFR-mutated NSCLC. Methods: Herein, we introduce our phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected NSCLC with EGFR mutation. Accrued patients will be pathological stage II–IIIA with completely resected NSCLC and whose tumors have EGFR mutation. Treatment comprises four cycles of cisplatin plus vinorelbine combined with atezolizumab followed by maintenance with atezolizumab. The primary endpoint is the disease-free survival (DFS) rate at 2 years. Secondary endpoints are DFS, overall survival, and safety. In total, 18 patients will be enrolled in this study. Discussion: Ongoing phase III trials of adjuvant ICI allow the inclusion of patients with EGFR mutation, but our current trial will provide the earliest clinical data on the efficacy of platinum-doublet chemotherapy with atezolizumab.

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