scholarly journals Exploration of resistance mechanisms for epidermal growth factor receptor‐tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain reaction and next‐generation sequencing

2018 ◽  
Vol 109 (12) ◽  
pp. 3921-3933 ◽  
Author(s):  
Eiji Iwama ◽  
Kazuko Sakai ◽  
Koichi Azuma ◽  
Daijiro Harada ◽  
Kaname Nosaki ◽  
...  
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Chain Reaction ◽  
Plasma Analysis ◽  
Epidermal Growth ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction ◽  
Generation Sequencing

scholarly journals Heterogeneity and Coexistence of T790M and T790 Wild-Type Resistant Subclones Drive Mixed Response to Third-Generation Epidermal Growth Factor Receptor Inhibitors in Lung Cancer

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Zofia Piotrowska ◽  
Mehlika Hazar-Rethinam ◽  
Coleen Rizzo ◽  
Brandon Nadres ◽  
Emily E. Van Seventer ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Third Generation ◽  
Chain Reaction ◽  
Liquid Biopsies ◽  
Epidermal Growth ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction

Purpose Third-generation epidermal growth factor receptor (EGFR) inhibitors like nazartinib are active against EGFR mutation–positive lung cancers with T790M-mediated acquired resistance to initial anti-EGFR treatment, but some patients have mixed responses. Methods Multiple serial tumor and liquid biopsies were obtained from two patients before, during, and after treatment with nazartinib. Next-generation sequencing and droplet digital polymerase chain reaction were performed to assess heterogeneity and clonal dynamics. Results We observed the simultaneous emergence of T790M-dependent and -independent clones in both patients. Serial plasma droplet digital polymerase chain reaction illustrated shifts in relative clonal abundance in response to various systemic therapies, confirming a molecular basis for the clinical mixed radiographic responses observed. Conclusion Heterogeneous responses to treatment targeting a solitary resistance mechanism can be explained by coexistent tumor subclones harboring distinct genetic signatures. Serial liquid biopsies offer an opportunity to monitor clonal dynamics and the emergence of resistance and may represent a useful tool to guide therapeutic strategies.

Successful retreatment with erlotinib after erlotinib-related interstitial lung disease

2021 ◽  
pp. 030089162110200
Author(s):  
Haci M. Turk ◽  
Mustafa Adli ◽  
Melih Simsek ◽  
Altay Aliyev ◽  
Mehmet Besiroglu
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Disease ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Background: Epidermal growth factor receptor tyrosine kinase inhibitors are effectively being used in the treatment of non-small cell lung cancer. Although most of their adverse effects are mild to moderate, they occasionally can cause life-threatening interstitial lung disease. We aimed to present a case of lung adenocarcinoma successfully re-treated with erlotinib after recovery with effective treatment of erlotinib-induced interstitial lung disease. Case description: A 54-year-old nonsmoking woman was diagnosed with metastatic adenocarcinoma of the lung. After progression with first-line chemotherapy, erlotinib 150 mg daily was initiated. On the 45th day of erlotinib treatment, interstitial lung disease occurred and erlotinib was discontinued. Clinical improvement was achieved with dexamethasone treatment and erlotinib was re-initiated. Ten weeks after re-initiation of erlotinib, 100 mg daily partial response was observed. Conclusions: Incidence of interstitial lung disease is higher in men, smokers, and patients with pulmonary fibrosis. Interstitial lung disease radiologically causes ground-glass opacity and consolidation. The physician should quickly evaluate new respiratory symptoms in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors, discontinue the epidermal growth factor receptor tyrosine kinase inhibitor treatment, and initiate corticosteroids if clinical diagnosis is interstitial lung disease.

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