Therapeutic Strategies in EGFR Mutant Lung Cancer

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Sun Yat-sen University Cancer Center (SYSUCC)

Tomoya Kawaguchi

Graduate School of Medicine, Osaka City University

First Affiliated Hospital of Guangzhou Medical University

Sun Yat-sen University Cancer Center (SYSUCC)

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Lung cancer, specifically non-small-cell lung cancer (NSCLC), remains the leading cause of cancer-related mortality worldwide. It has been shown that the EGFR-dependent pathway is activated in many patients with NSCLC. Small-molecule tyrosine kinase inhibitors (TKIs) are the preferred initial therapy for the treatment of EGFR mutant, advanced NSCLC.

First, second and third-generation EGFR-TKIs are currently approved for the treatment of patients with NSCLC that harbors a sensitizing EGFR mutation. Each TKI has its own characteristics influencing therapeutic efficacy and toxicity. While initially effective, acquired resistance to EGFR-TKI is expected and a small subset of patients exhibit primary resistance to EGFR-TKI therapy. The mechanisms underlying primary and acquired resistance to EGFR-TKI are increasingly complex, often including acquired mutations within the drug target, engagement of ‘bypass’ pathways, intra- and inter-tumoral heterogeneity, coexistent genetic alterations in other cancer-related genes, transformation to other histologic subtypes (squamous and small-cell lung cancer) and many others. A greater understanding of the underlying biology is needed to develop strategies to overcome or prevent TKI resistance. In addition, while immuno-oncology (IO) agents are emerging as an effective treatment option for many patients with NSCLC, outcomes in patients with EGFR mutant NSCLC have been disappointing. Additional research to develop IO therapeutic strategies in EGFR-mutant lung cancer is warranted.

This Research Topic is aimed at elaborating on the progress and controversy in translational and clinical research of EGFR mutant lung cancer. We welcome Original Research contributions, relevant Review articles, Perspective and Opinion articles and unique Case Reports, which are aimed at translational research, biological characteristics, genomics and transcriptomics analysis, epidemiology, diagnosis, drug resistance, new drug development, and prognosis for patients with EGFR mutant NSCLC.

Lung cancer, specifically non-small-cell lung cancer (NSCLC), remains the leading cause of cancer-related mortality worldwide. It has been shown that the EGFR-dependent pathway is activated in many patients with NSCLC. Small-molecule tyrosine kinase inhibitors (TKIs) are the preferred initial therapy for the treatment of EGFR mutant, advanced NSCLC.

First, second and third-generation EGFR-TKIs are currently approved for the treatment of patients with NSCLC that harbors a sensitizing EGFR mutation. Each TKI has its own characteristics influencing therapeutic efficacy and toxicity. While initially effective, acquired resistance to EGFR-TKI is expected and a small subset of patients exhibit primary resistance to EGFR-TKI therapy. The mechanisms underlying primary and acquired resistance to EGFR-TKI are increasingly complex, often including acquired mutations within the drug target, engagement of ‘bypass’ pathways, intra- and inter-tumoral heterogeneity, coexistent genetic alterations in other cancer-related genes, transformation to other histologic subtypes (squamous and small-cell lung cancer) and many others. A greater understanding of the underlying biology is needed to develop strategies to overcome or prevent TKI resistance. In addition, while immuno-oncology (IO) agents are emerging as an effective treatment option for many patients with NSCLC, outcomes in patients with EGFR mutant NSCLC have been disappointing. Additional research to develop IO therapeutic strategies in EGFR-mutant lung cancer is warranted.

This Research Topic is aimed at elaborating on the progress and controversy in translational and clinical research of EGFR mutant lung cancer. We welcome Original Research contributions, relevant Review articles, Perspective and Opinion articles and unique Case Reports, which are aimed at translational research, biological characteristics, genomics and transcriptomics analysis, epidemiology, diagnosis, drug resistance, new drug development, and prognosis for patients with EGFR mutant NSCLC.

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Editors

Sun Yat-sen University Cancer Center (SYSUCC)

Tomoya Kawaguchi

Graduate School of Medicine, Osaka City University

First Affiliated Hospital of Guangzhou Medical University

Sun Yat-sen University Cancer Center (SYSUCC)

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Frontiers in Oncology

Thoracic Oncology

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