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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
[Current status of EGFR/ErbB inhibitors in non-small cell lung carcinoma]
Carlos Álvarez-Fernández1, Emilio Esteban-González1
1Servicio de Oncología Médica, Hospital Universitario Central de Asturias, Oviedo, España.
Abstract:
In the last 10 years, there has been a major change in the treatment of lung cancer (LC). The discovery of activating mutations in the epidermal growth factor receptor (EGFR) in some histological subtypes of LC and its sensitivity to tyrosine kinase inhibitors (TKI) has represented a substantial advance in the treatment of this entity. Until then, the only available option to treat this type of tumour was based on chemotherapy, with a small but significant benefit in terms of survival and quality of life. The arrival of new agents that act against activating EGFR mutations gave rise to the era of precision medicine with targeted therapies able to act on the origin of the tumour, thus providing a therapeutic benefit while minimizing adverse effects and delaying administration of chemotherapy. In addition, this has produced a change in the diagnostic paradigm of lung cancer (as well as in that of all tumours), with a shift from a purely histological diagnosis to a classification of tumours based on their mutational characteristics. This shift has been made possible by the development of technologies allowing complex DNA analysis. Together with the efforts of researchers from all over the world, these techniques allow continued discovery of genetic alterations that could be the target of new drugs as well as definition of the mechanisms of activity and resistance to treatments. This extraordinary development of targeted therapies cannot change the fact that metastatic lung cancer continues to be an incurable disease and, at the present time, only a few patients will benefit from targeted therapies. Ongoing research will shed new light on the molecular alterations that give rise to LC and will provide new treatment alternatives for this disease.
Insights
Targeted therapies and EGFR mutations have revolutionized lung cancer treatment, shifting diagnosis towards molecular characteristics. While promising, metastatic lung cancer remains incurable, necessitating ongoing research for new alternatives.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer treatment has significantly evolved over the past decade.
- The discovery of EGFR mutations in specific lung cancer subtypes marked a paradigm shift.
Purpose of the Study:
- To review the advancements in lung cancer treatment driven by targeted therapies.
- To highlight the transition towards precision medicine and molecular-based diagnostics in lung cancer.
Main Methods:
- Review of recent literature on lung cancer treatment and targeted therapies.
- Analysis of the impact of EGFR mutation discovery and tyrosine kinase inhibitors (TKIs).
- Discussion of the evolving diagnostic landscape from histology to molecular profiling.
Main Results:
- Targeted therapies, particularly TKIs for EGFR mutations, offer improved outcomes and reduced side effects compared to traditional chemotherapy.
- Molecular profiling has become crucial for classifying lung cancer and guiding treatment decisions.
- Despite progress, metastatic lung cancer remains largely incurable, with limited patient benefit from current targeted therapies.
Conclusions:
- Precision medicine, driven by molecular diagnostics and targeted therapies, has transformed lung cancer care.
- Continued research into genetic alterations and resistance mechanisms is essential for developing novel treatments.
- Further investigation is needed to improve outcomes for all lung cancer patients, especially those with metastatic disease.
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