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Targeting the epidermal growth factor receptor in non-small cell lung cancer
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA. rherbst@mdanderson.org
Abstract:
Fifteen% or fewer of patients with non-small cell lung cancer (NSCLC) survive 5 years. The current standard of care for patients with locally advanced or metastatic NSCLC is systemic chemotherapy with a two-drug combination regimen that includes a platinum agent. Although systemic chemotherapy reduces the rate of death attributable to lung cancer, disease progression is inevitable and dose-limiting toxicities restrict their use. New molecularly targeted therapies aim to inhibit specific pathways and key molecules implicated in tumor growth and progression while sparing normal cells. Several therapies, which target signal transduction pathways involved in angiogenesis, metastasis, and apoptosis, are in clinical development to treat lung cancer. Among these targeted therapies are the oral, small-molecule epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors gefitinib and erlotinib. Both therapies have been validated preclinically as new treatment approaches for NSCLC and have shown single-agent activity against advanced, chemorefractory NSCLC in clinical trials. This article focuses on the biology of the EGFR-TK signal transduction pathway, its role in the proliferation of solid tumors, and the rationale for the clinical development of EGFR-TK inhibitors. We also review clinical trials with EGFR-TK inhibitors in NSCLC and future directions of investigation with these targeted agents.
Insights
New targeted therapies, like epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors, show promise for non-small cell lung cancer (NSCLC) treatment. These agents target tumor growth pathways, offering a new approach beyond traditional chemotherapy for advanced NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) has a poor 5-year survival rate, with current chemotherapy offering limited long-term benefit and significant toxicity.
- Systemic chemotherapy is the standard for advanced NSCLC but often leads to inevitable disease progression and dose-limiting toxicities.
- Novel molecularly targeted therapies are being developed to specifically inhibit pathways driving tumor growth and progression.
Purpose of the Study:
- To explore the biology of the epidermal growth factor receptor-tyrosine kinase (EGFR-TK) signaling pathway in solid tumor proliferation.
- To provide the rationale for the clinical development of EGFR-TK inhibitors as a targeted therapy for NSCLC.
- To review existing clinical trials involving EGFR-TK inhibitors in NSCLC and discuss future research directions.
Main Methods:
- Review of preclinical data validating EGFR-TK inhibitors as novel treatment approaches for NSCLC.
- Analysis of clinical trial data demonstrating single-agent activity of EGFR-TK inhibitors in advanced, chemorefractory NSCLC.
- Focus on the biological mechanisms of EGFR-TK signaling and its role in tumor proliferation.
Main Results:
- EGFR-TK inhibitors like gefitinib and erlotinib have shown preclinical validation and single-agent activity in advanced NSCLC.
- These targeted therapies aim to inhibit specific molecular pathways crucial for tumor growth, metastasis, and apoptosis.
- The development of EGFR-TK inhibitors represents a shift towards personalized medicine in NSCLC treatment.
Conclusions:
- EGFR-TK inhibitors offer a promising targeted approach for managing non-small cell lung cancer, potentially overcoming limitations of traditional chemotherapy.
- Understanding the EGFR-TK pathway is critical for developing effective targeted therapies.
- Continued clinical investigation of EGFR-TK inhibitors is essential to optimize their use in NSCLC treatment strategies.
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