CRUK Lung Cancer Centre of Excellence 2024

In 2014 there were few high-quality funding applications for lung cancer research with stagnation in progress contributing to poor outcomes.

The CRUK Lung Cancer Centre of Excellence (LCCE) was initiated in 2015 with sister sites in London (UCL) and Manchester to strengthen and coordinate UK multidisciplinary lung cancer research as a strategic priority.

We anticipated within a decade we would demonstrably accelerate UK lung cancer research and strongly believe that this has been achieved.

We developed an efficient structure of interlinked themes in Basic Science, Prevention/Early Detection/Pre-invasive Disease, Immunology and Clinical Trials, supported by specialised cores in Clinical Translation and Biomarkers, Pathology, Informatics and Preclinical Models.

LCCE impacts include our highly cited publications, a broad portfolio of clinical trials (ten practice changing), computational biology insights and tools and a preclinical model biobank available to the research community.

Our pioneering efforts in community based LDCT screening led to the approval of a National Lung Cancer Screening Programme.

The LCCE became a magnet for pharmaceutical and biotech company partnerships, meaningfully contributed to a spin-out company and attracted global lung cancer stars as collaborators.

We prioritised training of lung cancer researchers, with 55 students gaining LCCE PhDs as a powerful springboard to next career steps. Many LCCE young investigators obtained independent fellowships with >15 new PIs arising from LCCE training. Junior and senior LCCE investigators have garnered international prizes.

We have been nimble in our approach to the changing landscape of lung cancers, pivoting towards precision prevention approaches, whilst maintaining efforts on late-stage disease treatment optimisation with focus on improved approaches to targeted and immunotherapies, risk of disease relapse biomarkers and biomarker-driven clinical trials with fully embedded patient and public involvement and engagement.

Since 2019, we published >480 publications with 72 co-authored across the synergistic sister sites.

Our research highlights include discovery of a role for pollution-induced inflammation in promoting NSCLC, mapping molecular landscapes of precancerous airway lesions, defining immunological predictors of lesion progression and a comprehensive portfolio of papers characterising lung cancer evolution.

We developed a suite of biomarkers for risk of NSCLC relapse post-surgery and identified metastasis forming subclones.

We made important discoveries in understanding cancer cachexia and reducing cardiac toxicity associated with thoracic radiotherapy.

In SCLC, we generated unique patient-derived models to study biology and test novel therapeutics, demonstrated functional plasticity whereby tumour cells generate their own blood vessels and developed a blood test to subtype SCLC for upcoming stratified medicine trials.

The LCCE also developed 15 computational tools, including analysis of T cell content from whole exome sequencing data, an AI tool for grading LUADs and a ctDNA methylation profiling pipeline for application in liquid biopsy early detection and disease monitoring.

Supported by our 4 cores, we will more intimately link our early detection and immunology themes, focus on multi-analyte biomarker assessment holistically combining tumour intrinsic and microenvironmental features in blood, define molecular insults driving normal epithelia to invasive cancer and discover mechanisms of early cancer development for targeted prevention.

We will predict, track and target immune failure in late-stage NSCLC immunotherapy and seek understanding of immune evasion in SCLC.

Our basic scientists will study NSCLC initiation, continue their outstanding work on tumour evolution (chromosome instability, plasticity, immune evasion and replication timing), evaluate new targeted therapies in our NSCLC and SCLC preclinical models, decipher tropism during SCLC dissemination and examine the contribution of innervation to SCLC behaviours.

We are leading national trials (>45 trials since 2019) and will continue to drive innovative trial designs, maximising our globally leading position in proton therapy.

Several flagship trials will progress, including the mesothelioma proton trial HIT-MISO, the CONCORDE platform trial of DNA damage response inhibitors combined with radiotherapy in NSCLC and ADEPTT which extends opportunity for targeted therapy using the KRAS G12C inhibitor in the elderly or patients with poor performance status.

We will grow our national and international networks, expand the LCCE with new members, set up a LCCE alumnus global network, repeat our hugely successful young investigator workshop and host the next 2 lauded CRUK LCCE conferences, and redouble our efforts to make our research inclusive and equitable for all, amplifying our input from patients and carers, to drive the next generation of research scientist and discoveries to improve outcomes.