We investigate the processes controlling lung cancer formation and progression and aim to develop new methods of early lung cancer detection, staging and treatment.
Programme leader: Professor Sam Janes
Lung cancer biology
Pre-invasive lung cancer
Lung cancer is the leading cause of cancer-related deaths worldwide. Around one third of lung cancer cases arise from precancerous lesions in the airway epithelium. However, only around half of these lesions progress to incurable invasive cancer, while the rest remain stable or even disappear.
A primary goal of our research is to understand the biological processes that cause precancerous cells in the human airways to progress into incurable invasive lung cancer.
We have recently discovered molecular differences between lesions that progress to cancer and lesions that disappear. We are investigating how these alterations affect the properties of airway epithelial cells and their interaction with their microenvironment. We aim to identify key genes whose malfunction promotes invasive behaviour in precancerous cells. This work fits our clinical interest in monitoring a large cohort of patients with pre-invasive lung cancer lesions.
Mesothelioma is a cancer of the lung's lining for which current treatment options are limited. In collaboration with Ultan McDermott's lab in the Wellcome Trust Sanger Institute we investigated whether mutations commonly seen in mesothelioma affect how the cancer would respond to different drugs. We discovered that mesothelioma cells with mutations in BRCA associated protein-1 (BAP1) are sensitive to the anti-cancer drug TRAIL (TNF-related apoptosis-inducing ligand).
Since BAP1 is the most common mutation in mesothelioma, our findings may lead the way to a new treatment approach.
Early cancer diagnosis
Identification of an infrared spectral biomarker of lung cancer risk
We have found that using infrared spectroscopy we could detect changes in healthy cheek cells that indicate the presence of a distal lung cancer. With support from the Roy Castle Lung Foundation, we are further developing this work to identify a novel way to detect lung cancer through a cheek (buccal) swab.
A soft brush, with similar sensation to a toothbrush is rotated on the inside of the cheek to take the sample. Cheek cells are prepared and placed on a slide, which is analysed using infrared light. Initial results are once again promising and show that we can differentiate between individuals with cancer and those without from this simple non-invasive sampling. This research has exciting potential to be used as an early screening tool for lung cancer with the aim of improving the early diagnosis of lung cancer. We are currently expanding recruitment and validating our analysis.
Lung Cancer Indicator Detection (LuCID) Trial
Lungs for Living is coordinating the UCL/UCLH participation in the LuCID 2 Trial, conducted by Owlstone Medical. This is a multi-centre prospective phase II trial, investigating the diagnostic accuracy of a breath test to detect lung cancer, with a view to improving early diagnosis. The study has been recruiting since 2015.
Further information about this trial can be found at: LuCID Trial
Developing new anti-cancer therapies
We are investigating the potential of using stem cells to deliver anti-cancer therapies. Through rational integration of fundamental, translational and clinical studies from our team, we are taking this novel therapy from bench to bedside.
Our successful pre-clinical projects funded by the Wellcome Trust, examined the use of modified stem cells to deliver the anti-cancer drug TRAIL to tumours. This led to the TACTICAL trial, funded by the Medical Research Council (MRC). TACTICAL is a first in man clinical trial looking at the use of these genetically modified stem cells for the treatment of advanced lung cancer. The trial is now open and recruiting patients into phase I.
ClinicalTrials.gov Identifier: NCT03298763
Some of our latest research papers:
- Immune surveillance in clinical regression of pre-invasive squamous cell lung cancer. Cancer Discov (2020) July 20; CD-19-1366
- Tobacco smoking and somatic mutations in human bronchial epithelium. Nature (2020) 578, 266-272
- Deciphering the genomic, epigenomic and transcriptomic landscapes of pre-invasive lung cancer lesions. Nat Med (2019) 25, 517-525
- The potential of breath analysis to improve outcome for patients with lung cancer. J Breath Res (2019) April 24
- Impact of a Lung Cancer Screening Information Film on Informed Decision-Making: A Randomized Trial. Ann Am Thorac Soc (2019) May 13
- Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells. Elife (2018) 7:e30224