Why we focus on lung cancer
Lung cancer is the third most common cancer in the UK, with around 47,800 new lung cancer cases diagnosed in the UK every year. Lung cancer has one of the lowest survival outcomes of all cancers because over two-thirds of patients are diagnosed at a late stage when curative treatment is not possible. When diagnosed at its earliest stage, 57% of people with lung cancer will survive their disease for five years or more, compared with only 3% when the cancer is diagnosed at the latest stage.
Workplace exposures are linked to 13% of lung cancer cases in the UK, a large proportion of these due to asbestos resulting in a cancer of the lining of the lungs called mesothelioma. Our researchers are combining both basic molecular biology and clinical research to advance our understanding and treatment of lung cancer.
We are investigating the early events that initiate lung cancer, such as loss of the tumour suppressor gene LIMD1.
We are looking at aberrant tumour metabolism and inflammation in mesothelioma and how this can be exploited in the clinic. Based on our preclinical studies we are now testing whether arginine deprivation will herald a new approach in treating patients with lung cancers (ADAM and TRAP clinical trials).
We are identifying new therapeutic strategies for treatment of mesothelioma patients using a synthetic lethal approach.
We are investigating how lung cancer spreads which will help us to identify and design new therapies to prevent this spread and metastasis. We believe this multi-disciplinary approach to lung cancer research will have a real impact on patient health.
Click on the links below to find out which researchers are working on:
Patients and Carers: Please click here to visit the CRUK website for more information on lung cancer
Major Funders	Key Publications
Barts Charity
British Lung Foundation
Medical Research Council
Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1–Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms. JTO Clinical and Research Reports (2020) https://doi.org/10.1016/j.jtocrr.2020.100093.
A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. EMBO Mol Med (2018) PMID: 29930174
Arginine Deprivation With Pegylated Arginine Deiminase in Patients With Argininosuccinate Synthetase 1-Deficient Malignant Pleural Mesothelioma: A Randomized Clinical Trial. JAMA Oncol (2017) 3(1):58-66. PMID: 27584578
The LIMD1 protein bridges an association between the propyl hydroxylases and VHL to repress HIF-1 activity. Foxler et al. Nat Cell Biol (2012) 14:201-8. PMID: 22286099
The chromosome 3p21.3-encoded gene, LIMD1, is a critical tumor supressor involved in human lung cancer development. Sharp et al. Proc Natl Acad Sci (2008) 105: 19932-7. PMID: 19060205
Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase. Szlosarek et al. J Clin Oncol (2013) 31:111-3. PMID: 23319692
In vivo loss of expression of argininosuccinate synthetase in malignant pleural mesothelioma is a biomarker for susceptibility to arginine depletion. Szlosarek et al. Clin Cancer Res (2006) 12:7126-31. PMID: 17145837
ERK2 but not ERK1 mediates HGF-induced motility in non small cell lung carcinoma cell lines. Radtke et al. J Cell Sci (2013) 126(Pt 11):2381-91. PMID: 23549785
A direct role for Met endocytosis in tumorigenesis. Joffre et al. Nat Cell Biol (2011) 13:827-37. PMID: 21642981
Image credit: Lung cancer cells. Anne Weston, Francis Crick Institute. CC BY-NC
Adhesion and Integrins
Blood cancers
Cancer Bioinformatics
Cancer Gene Therapy
Cancer Imaging
Cancer-related Inflammation
Cell Signalling
Metastasis and Invasion
RNA Biology
Tumour Microenvironment