Current research

We have a comprehensive research program that involves laboratory investigation with a strong theme of developing new treatments for lung cancer and understanding the processes causing and controlling the disease. We also have a track record of delivering high quality clinical research projects involving the early diagnosis and staging of patients with lung cancer, the main themes are summarised below along with examples of current projects:

Understanding how lung cancer starts

  • Lung homeostasis and stem cell biology
  • Studies of changes in DNA
  • Novel molecular mechanisms

Diagnosing and staging of lung cancer

  • Endobronchial Ultrasound (EBUS)
  • The LungSEARCH trial
  • Changes in gene expression
  • Field cancerisation

Developing new treatments for lung cancer

  • Stem cell therapy
  • Photodynamic therapy

Airway regeneration

  • Replacing diseased airway

Understanding how lung cancer starts

Lung homeostasis and stem cell biology

We have found that by measuring the size of patches of cells within the airway harbouring specific mutations we are able to determine the specific stem or progenitor cells that maintain the airway in health and also the impact of tobacco smoke exposure and ageing on airway maintenance.

Studies of changes in DNA

Over the last 15 years we have been collecting lung biopsy samples in our research biobank which have come from patients who have pre-cancerous changes within the airways and are at very high risk of developing lung cancer. We are looking at the difference in methylation profiles of DNA in these samples comparing normal airway with pre-cancerous lesions and also between those lesions that progress to invasive cancer versus those that spontaneously resolve.

Novel molecular mechanisms

The early events in lung cancer formation are likely to hold the key to developing new treatments, we have previously identified beta-catenin and Lrig1 as having pivotal roles. We are currently investigating a molecule called Cadm1 (cell adhesion molecule 1) in the early initiation of lung cancer.

Diagnosing and staging lung cancer earlier

Endobronchial Ultrasound (EBUS)- 'BOOST' study (Bronchoscopic or Oesophageal ultrasound for lung cancer staging)

This is the first randomised controlled trial of EBUS (link to page explaining EBUS) as a first test in the diagnosis and staging of non-small cell lung cancer. The study tests the hypothesis that EBUS as an initial diagnostic and staging tool can reduce the delay in diagnosing lung cancer and reduce the number of other investigations required including surgical diagnostic procedures. The results will have an impact on clinical practice and lung cancer guidelines; it has now been successfully completed and is submitted for publication.

The Lung SEARCH study

This is a multicentre trial that has recruited 1300 patients and is currently in the follow-up phase. It is a randomised controlled trial of surveillance for the early detection of lung cancer in an at risk group (patients with chronic obstructive pulmonary disease). The trial uses autofluorescence bronchoscopy (white and blue light), spiral CT and sputum cytology/cytometry to pick up very early lung

Gene expression profiling

At UCLH we have a unique cohort of patients who have pre-cancerous changes within in the main airways which represent the very earliest stages of the pathway towards invasive lung cancer. Understanding the processes that initiate these lesions and lead to subsequent cancer formation are key to developing new techniques for early diagnosis and treatment. One of our strategies is to look at alterations in gene expression and how this differs between lesions that spontaneously regress and those that develop into an invasive cancer.

Field cancerisation- SPECTRAL study

Tobacco smoke exposure causes a 'field of damage' throughout the lungs, nose and mouth and although the cells lining these organs remain normal when viewed down a microscope they harbour minute changes in their architecture, gene expression and metabolism. We are using novel optical technology including Infrared spectroscopy and elastic scattering spectroscopy to detect these changes which we hope to develop into a high through-put non-invasive screening tool for identifying those most at risk of developing lung cancer.

Developing new treatments for lung cancer

Stem cells

Mesenchymal stem cells (MSC's) have been extensively researched by ourselves and others and shown to have the ability to home directly to tumours when injected or viewed under a microscope, uniquely they don't cause an immune reaction and are therefore ideal for cellular therapy- meaning that they can be used to deliver drugs directly to a tumour without causing damage to normal tissues.

We have shown that MSC's modified to express TRAIL (TNF-related apoptosis-inducing ligand) can in the laboratory effectively treat cancer. The mechanisms governing stem cell homing to tumours is also a major research theme within our laboratory.

Photodynamic therapy (PDT)

Photodynamic therapy is a treatment using a drug that causes cancer cells to undergo cell death when exposed to laser light of a specific wavelength. It has been shown to be useful for the treatment of early cancer in many organs including the lung. We plan to use PDT to treat pre-cancerous lesions to prevent invasive lung cancer from developing in the context of a randomised control trial (PEARL trial) (link to future section)

Airway regeneration

Benign diseases that lead to the airways becoming abnormally narrowed cause very significant symptoms and until recently have had very few treatment options. We are part of a group at UCL and beyond who are working together to provide a solution. We aim to generate a fast an efficient method for transplanting an airway to replace the diseased section the will be coated with the patient's own cells within our laboratory prior to the operation. This will mean that the transplanted segment will function as normal and not be rejected by the patient's immune system.