Genetics and biomarkers in personalisation of lung cancer treatment

Non-small-cell lung cancer is often diagnosed at the metastatic stage, with median survival of just 1 year. The identification of driver mutations in the epidermal growth factor receptor (EGFR) as the primary oncogenic event in a subset of lung adenocarcinomas led to a model of targeted treatment an...

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Bibliographic Details
Published in:The Lancet (British edition) 2013-08, Vol.382 (9893), p.720-731
Main Authors: Rosell, Rafael, Dr, Bivona, Trever G, MD, Karachaliou, Niki, MD
Format: Article
Language:English
Subjects:
adenocarcinoma
Apoptosis - genetics
Biological and medical sciences
biomarkers
Biomarkers, Tumor - genetics
Carcinoma, Non-Small-Cell Lung - diagnosis
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - therapy
epidermal growth factor receptors
General aspects
Genes
Genes, Neoplasm - genetics
Genetic Markers - genetics
Genetics
high-throughput nucleotide sequencing
Humans
Internal Medicine
Kinases
Lung cancer
lung neoplasms
Lung Neoplasms - diagnosis
Lung Neoplasms - genetics
Lung Neoplasms - therapy
Medical research
Medical sciences
metastasis
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Mutation
Mutation - genetics
patients
Pharmaceutical industry
Pneumology
Precision Medicine - methods
remission
signal transduction
Signal Transduction - genetics
Tumors
Tumors of the respiratory system and mediastinum
tyrosine
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Summary:Non-small-cell lung cancer is often diagnosed at the metastatic stage, with median survival of just 1 year. The identification of driver mutations in the epidermal growth factor receptor (EGFR) as the primary oncogenic event in a subset of lung adenocarcinomas led to a model of targeted treatment and genetic profiling of the disease. EGFR tyrosine kinase inhibitors confer remission in 60% of patients, but responses are short-lived. The pre-existing EGFR Thr790Met mutation could be a subclonal driver responsible for these transient responses. Overexpression of AXL and reduced MED12 function are hallmarks of resistance to tyrosine kinase inhibitors in EGFR-mutant non-small-cell lung cancer. Crosstalk between signalling pathways is another mechanism of resistance; therefore, identification of the molecular components involved could lead to the development of combination therapies cotargeting these molecules instead of EGFR tyrosine kinase inhibitor monotherapy. Additionally, novel biomarkers could be identified through deep sequencing analysis of serial rebiopsies before and during treatment.
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(13)61715-8