The aim of the LLP is to reduce lung cancer mortality by developing and implementing a molecular-epidemiological risk assessment model and markers of pre-clinical carcinogenesis. The success of the LLP programme may be measured not only by its publication record but also the ability to attract significant funding from UK (CR-UK, NIHR, PCTs), EU (FP5, FP7) and USA (NIH) as well as establishing strategic collaborations with academic and industrial partners, to undertake complementary studies in early lung cancer detection.
The current LLP objectives are:
To redefine pathology of lung cancer based on its molecular signatures, determined by genome-wide expression and methylation, miRNA profiling and next generation sequencing.
To prepare the next iteration of the Liverpool Lung Project Risk Assessment Model incorporating validated biomarkers and providing an improved algorithm to measure an individual’s 5-year absolute risk of developing lung cancer.
To develop an early lung cancer detection biomarker roadmap which is integrated into the assessment of high risk individuals.
Maintain and expand the archive of specimens for at-risk individuals and those with lung cancer for biomarker discovery and validation.
Facilitate the development of new intervention strategies for high risk individuals.
Long non-coding RNA (lncRNA) profiles change dramatically in non-small cell lung cancer (NSCLC).
A new research study published by Roy Castle Lung Cancer Research Foundation scientist provides new insights into the range of molecular abnormalities underlying the pathogenesis of NSCLC. The study was published in British Journal of Cancer on 5 Feb 2020 and utilised a massive screening of long non-coding RNAs in a large number of lung tumours, demonstrating that over 6,000 lncRNA genes are highly dysregulated, i.e. produced in higher or lower amounts compared to normal lung cells.
lncRNAs compose a class of genes that do not encode a protein as the “classical” coding genes. While the first such gene in humans was discovered in 1989, it was only after 2010 that the field saw an explosive expansion with the understanding of their involvement in human disease, among which cancer. As a relatively new class of genes, it is under-researched; we only understand the function of a small minority of a total exceeding 15,000 of these genes. However, current research has shown that lncRNAs do not transfer genetic information within the cell (as the “classical” genes would do); instead, they exhibit a wide range functions, including the regulation of other genes, serving as scaffolds for protein complexes etc.
A group of scientists of the Roy Castle Lung Cancer Research Programme in the University of Liverpool screened a large number of lung tumours for the presence of these lncRNAs and reported a list of over 6,000 genes to be abnormally produced. The team, led by Dr Lakis Liloglou, subsequently comparatively analysed the findings to a central database (TCGA – The Cancer Genome Atlas Program of the National Cancer Institute in the USA) in order to validate the results and compare to lung tumours from different countries.
This discovery opens new avenues for identifying biomarkers for the clinical management of lung cancer. The research team is currently preparing the plan for the next steps to translate the findings into clinically useful information. The most potent task currently is to test whether the highly overexpressed lncRNAs in lung tumours can be detected in the blood, therefore assisting early detection. The team has access to the precious Biobank of the Liverpool Lung Project, funded by the Roy Castle Lung Cancer Foundation, which enables such studies and the Liverpool team is intending to start the new work by summer 2020.
The published paper can be found in (https://www.nature.com/articles/s41416-020-0742-9)