Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in EGFR -mutant non-small cell lung cancer: A new era begins

• Published in: Cancer treatment reviews 2014-02, Vol.40 (1), p.93-101
• Main Authors: Remon, J, Morán, T, Majem, M, Reguart, N, Dalmau, E, Márquez-Medina, D, Lianes, P
• Format: Article
• Language: English
• Subjects: Acquired resistance; Animals; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Drug Resistance, Neoplasm; EGFR-mutant tumors; Gene Amplification; Gene Expression; Hematology, Oncology and Palliative Medicine; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Medical sciences; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Non-small cell lung cancer; Pharmacology. Drug treatments; Pneumology; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Proteins c-met - genetics; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction; Tumors; Tumors of the respiratory system and mediastinum; Tyrosine kinase inhibitors
• ISSN: 0305-7372; 1532-1967
• DOI: 10.1016/j.ctrv.2013.06.002

Abstract The discovery of mutated oncogenes has opened up a new era for the development of more effective treatments for non-small cell lung cancer patients (NSCLC) harbouring EGFR mutations. However, patients with EGFR -activating mutation ultimately develop acquired resistance (AR). Several studies have identified some of the mechanisms involved in the development of AR to EGFR tyrosine kinase inhibitors (TKI) that can be potential therapeutic strategies, although in up to 30% of cases, the underlying mechanism of AR are still unexplained. In this review we aim to summarize the main mechanisms of AR to EGFR TKI and some clinical strategies that can be used in the daily clinical practice to overcome this resistance and try to prolong the outcomes in this subgroup of patients.