Translating the transcriptome into tools for the early detection and prevention of lung cancer: Figure 1

Abstract

Despite advances in the management of lung cancer, this disease remains a significant global health burden with survival rates that have not significantly improved in decades. The mortality reduction achieved by low-dose helical CT (LDCT) screening of select high-risk patients is challenged by the high false positive rate of this screening modality and the potential for morbidity associated with follow-up diagnostic evaluation in patients with high risk for iatrogenic complications. The diagnostic dilemma of the indeterminate nodule incidentally identified on diagnostic or screening CT has created a need for reliable biomarkers capable of distinguishing benign from malignant disease. Furthermore, there is an urgent need to develop molecular biomarkers to supplement clinical risk models in order to identify patients at highest risk for having an early stage lung cancer that may derive the greatest benefit from LDCT screening, as well as identifying patients at high-risk for developing lung cancer that may be candidates for emerging chemopreventive strategies. Evolving bioinformatic techniques and the application of these algorithms to analyse the transcriptomic changes associated with lung cancer promise translational discoveries that can bridge these large clinical gaps. The identification of lung cancer associated transcriptomic alterations in readily accessible tissue sampling sites offers the potential to develop early diagnostic and risk stratification strategies applicable to large populations. This review summarises the challenges associated with the early detection, screening and chemoprevention of lung cancer with an emphasis on how genomic information encapsulated by the transcriptome can facilitate future innovations in these clinical settings.

Early Events in the Molecular Pathogenesis of Lung Cancer

“…Despite encouraging findings from the National Lung Screening Trial (142,143), early detection of lung cancer is challenging due to the lack of biomarkers for the early diagnosis of the disease and due to the presence of multiple neoplastic molecular pathways that mediate lung carcinogenesis (5,18,103,114). Moreover, little progress has been made in personalized and targeted chemoprevention strategies for this fatal malignancy (6,17).…”

Bronchialkarzinomscreening – Risikostratifizierung

“…Experimentelle Ansätze konnten zeigen, dass Genanalysen des Nasalepithels von Rauchern als Surrogatparameter dienen könnten, um den schadhaften Effekt des Rauchens auf die Lunge zu beurteilen [30]. Die Entwicklung von Biomarkern und Risikogenen tritt somit zunehmend in den Fokus der Forschung, und die laufenden Screeningstudien könnten beitragen, hier in den kommenden Jahre weitere Fortschritte zu erzielen [8,9]. …”

Year in review 2014. Paediatric and adult clinical studies

“…Other new outcome measures including a new symptom scale for patients with COPD suitable for daily use;47 a scoring system capable of predicting survival in patients with malignant pleural effusions;48 a lung-transplant specific quality of life score49 and an ultrasonic technique for assessing diaphragmatic thickness and likelihood of successful weaning in patients requiring mechanical ventilation 50. The radiographic pattern of connective tissue disease-associated interstitial lung disease was shown to be heterogeneous by Saketkoo et al 51 Understanding this heterogeneity is a priority before progress can be made with treatment, as is the identification of potential outcome measures.…”