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Thoracic Research Centre
Research Projects
Neuroendocrine Lung Cancers – Prof Kwun Fong
This project aims to study the molecular changes in this under-studied cancer of the lung,
to learn about the genomic landscape in these cancers which include carcinoids, large cell
neuro-endocrine and small cell lung cancers
Patient Perception of Lung Disease Screening and Management – Prof Kwun Fong
Effective patient communication is a key aim of high quality care in lung disease
management including surgery. Furthermore, community and patient preferences are vital
to understanding how best to translate new research findings to the community. This
project will survey patients to understand their perception of clinical messages and identify
tools to enhance patient and carer communication. It will also survey community and
patient attitudes in terms of lung cancer screening and treatment.
Biomarkers for Lung Cancer – Prof Kwun Fong
This project seeks to determine the potential use of liquid biopsies and minimally invasive
body fluids (blood, urine, bronchial washings, sputum) to enable the detection of lung
cancer biomarkers using state of the art technologies.
Lung Cancer Whole Genome Sequencing – Prof Kwun Fong
Lung cancer is the biggest cause of cancer deaths in Western countries including
Australia with smoking accounting for 85-90% of lung cancers. In the remainder, the
specific aetiology is uncertain with passive smoking, asbestos, cooking fumes and other
carcinogens implicated in some cases. Never smoking lung cancers are enriched for
specific somatic gene mutations such as EGFR exon 19 and 21 sensitising mutations,
EML4/ALK fusion mutations and both represent effective therapeutic targets. We
collaborated with the International Cancer Genome Consortium and The Cancer Genome
Atlas (TCGA) is to identify other relevant driver mutations by interrogation of the genome
by supplying high quality resected lung cancer tissues (adenocarcinoma and squamous
cell carcinoma). We seek to complement this work by undertaking genomic analysis of
never smoking adenocarcinomas in order to identify other therapeutic targets.
Epigenetic Profiling of Lung Adenocarcinoma from Never Smoking Patients – Prof
Kwun Fong
Lung cancer is thought to be due to the accumulation of insults to cells. Lung cancer in
patients who have never smoked may have different causative cellular changes from
those demonstrated in tumours that develop under the influence of a specific carcinogen,
such as tobacco cigarette smoke. This study examines the genetic code of cancers from
patients who have never smoked. DNA will be obtained from samples available from both
The Prince Charles Hospital Tissue Bank and international collaborators, and processed
by new techniques available to study the human genome. This will provide a list of
changes to the gene code that may contribute to lung cancer development in never
smokers. A second processing technique will be used to confirm these
findings. Subsequent studies will determine the effects of these changes, and whether
they are useful in diagnostic tests for lung cancer or as targets for treatment.
Genetic Mutation Testing in Clinical Practice – Prof Kwun Fong
Lung cancer is the biggest cause of cancer deaths in Australia and the world. Scientific
advances are allowing us the technically measure these genetic mutations that lead to
lung cancer with relative ease and accuracy, but lagging behind is the clinical translation
to actual patient benefit. Here we address the challenge in translating these innovations
to practice, by testing genetic mutations in samples obtained during diagnostic testing,
compared to lung cancer surgery specimens.
Treatment-Responsive Mutation Testing in Lung Cancer – Prof Kwun Fong
Lung cancer is a leading cause of cancer death and disease burden in many countries
including Australia. Understanding the biological pathways involved in lung cancer is
required to identify key biomolecules that could be of significant clinical value, either
through serving as predictive, prognostic or diagnostic markers, or as targets for the
development of novel therapies to treat this disease.
It is well-recognised that 'EGFR' mutation testing is a biomarker that has direct clinical
relevance to patients with lung cancer. Patients who have demonstrated EGFR mutations
in their lung cancer tissue are eligible for specific treatments that target these mutations
i.e. treatment with specific inhibitors, that potentially improve survival when used. This
study will therefore test the feasibility and diagnostic accuracy of undertaking biomarker
mutation testing during routine treatment of patients.
Multidisciplinary Lung Cancer Care – Prof Kwun Fong
It is well accepted that lung cancer care is optimally provided by an expert multidisciplinary
team comprising different specialties in achieving the best outcomes for our patients. This
project seeks to investigate and determine how to enhance key aspects of MDT care and
the lung cancer journey.
Low Dose CT Screening for Lung Cancer – Dr Henry Marshall and Dr Steven Leong
Lung cancer is the biggest cause of cancer deaths globally including Australia. Patients
often present at a late stage when curative intent treatment is no longer applicable. Lung
cancer screening efforts by CXR and sputum testing are ineffective. NLST, the US
National Lung Screening Trial, compared low-dose computed tomography (LDCT) and
standard chest X-ray, found that low-dose computed tomography screening statistically
significantly reduced lung cancer mortality by 20% in high-risk individuals.
In Queensland, our current LDCT observational screening study based on the NLST
design, has identified 10 lung cancers in 256 high-risk participants. All cancers occurred
in participants with impaired lung function in addition to the inclusion criteria set by the
NLST. CIs MT, SL and AM also found that lung cancer risk increased with decline in
FEV1% in a British Columbia Cancer Agency study of high-risk individuals enrolled and
followed prospectively. Using data from the Prostate, Lung, Colorectal, and Ovarian
Cancer Screening Trial PLCO, CI MT has developed and validated 2 lung cancer risk
prediction models.
These studies collectively indicate that accurate lung cancer risk prediction using patient
information and lung function tests can more precisely identify the population most likely to
benefit from LDCT screening. In this way, both the efficiency and cost-efficiency of LDCT
screening programs can be improved and possible harms from false positive screens be
reduced. In this 2nd phase of our LDCT research program, we will collaborate with our
Canadian colleagues to prospectively validate these models in a multicentre study.
A Novel X-ray Technique to find Lung Nodules – Prof Kwun Fong
Spots on the lung are an increasingly common finding, whether intentional or incidental,
due to the widespread use of computed tomography (CT) scanning and renewed interest
in screening for lung cancer using low dose CT. Many of these spots are too small to
biopsy or be seen on chest X-ray. There is a small possibility that these spots represent
early lung cancer.
Digital tomosynthesis (DT) is a new X-ray technique that exposes patients to
approximately 2% of the radiation of a CT scan and is at least 50% cheaper. Research
indicates that DT may be as good as CT, and significantly better than CXR, at detecting
lung spots. This project aims to formally compare the nodule detection ability of CXR and
DT, using CT scan as the reference standard. We predict that DT will detect nodules and
measure their dimensions as accurately as CT scan.
Cost Impact of Electromagnetic Navigational Bronchoscopy (ENB) for Lung Cancer
– Prof Kwun Fong
Currently people with distant lung cancer are often diagnosed with invasive method due to
the inability to reach the lesion and take lung tissue samples. Electromagnetic navigational
bronchoscopy (ENB) could potentially provide a similar effective, but less invasive, way for
obtaining lung tissue samples thus is safer than the current methods.
Before introducing ENB into the healthcare system in a large scale, it has to be proven to
be, firstly, useful and safe in detecting lung cancer. Secondly, the cost of using ENB has
to be justified when compared with the current methods used, whether with an increased
cost, similar cost or decreased cost. This project aims to evaluate value for money of ENB
by looking at the cost of using ENB for diagnosis of distant lung cancer taking into
consideration of its usefulness in detecting distant lung cancers.
The Journey of Rural and Urban Patients with Suspected Lung Cancer – Prof Kwun
Fong
Lung cancer is the leading cause of cancer-related mortality in Australia. We suspect that
the journey of patients with suspected lung cancer referred to a tertiary hospital is different
between non-urban and urban patients. To address this issue, we will follow patient
journeys for people referred with suspected lung cancer, both from urban and non-urban
centres. We will identify differences in logistical and psychosocial factors, and quality of
life impact, of people undergoing diagnostic evaluation. We will then be able to use these
observations to improve reversible factors that impact on this journey on patients.
Pet Scans for Lung Cancer – Prof Kwun Fong and Assoc/Prof Rayleen Bowman
Positron Emission Scans are indispensable for the management of lung and other
cancers. PET scans are typically used to the evaluation of lung nodules and staging of
lung cancers. This project will evaluate the optimal place (timing and sequence) of PET
and CT scan in the management of suspected and diagnosed lung cancer.
Biomarkers of Severity, Recovery and Recurrence of COPD Exacerbations – Prof
Ian Yang
Chronic obstructive pulmonary disease (COPD) is an incurable disease characterised by a
persistent blockage of airways from the lungs. Patients with COPD are occasionally
afflicted with acute exacerbations (AECOPD), which result in a worsened health status,
accelerated lung function decline and reduced survival. Hospitalisation of these patients
costs hundreds of millions of dollars each year and the symptoms are not adequately
explained by clinical, pathophysiological or health care factors. Thus, a better
understanding is needed of the factors that determine severity, rate of recovery and
recurrence of exacerbations. As respiratory infections are the major trigger, it is plausible
that inflammatory biomarkers are highly relevant. Early detection of these biomarkers in
blood and serum can be used to predict severity, recovery and recurrence of AECOPD,
which could then influence management of this disease.
Interventions against air pollution – Prof Ian Yang
Adverse health effects from air pollutants remain important, despite improvement in air
quality in the past few decades. While it is imperative to contain rising levels of air
pollution, it is also important that strategies be developed to minimise the damaging
effects of air pollutant exposure on the lung, especially for patients with chronic lung
disease. Diesel exhaust particles are increasingly recognised as a toxic component of air
pollution, leading to inflammation and other injury in the lungs. This project will investigate
interventions against the toxicity of diesel air pollutants exposed to bronchial cells tested in
the laboratory.
Genetic and Epigenetic changes in COPD and Increased Susceptibility to Lung
Cancer – Prof Ian Yang
Chronic obstructive pulmonary disease (COPD) is a potentially fatal chronic lung disease
with no currently available cure. Amongst the mechanisms potentially involved with
COPD, epigenetic modifications (changes to gene expression without direct alteration to
the DNA sequence), including DNA methylation, in the lungs could provide the basis for
many of the altered biological pathways in COPD. Environmental factors such as smoking,
diet, air pollution and infection all affect DNA methylation patterns and therefore patterns
of gene expression, with potential implications for the ageing lung. It is known that: 1. DNA
methylation status alters gene expression; 2. Changes in DNA methylation occur with
COPD; and 3. Changes in mRNA expression occur in COPD lung. We aim to discover
clinically relevant alterations in gene expression that could prove useful for risk
stratification and development of new therapeutic targets for COPD through correlation of
transcriptome sequencing and gene methylation profiles, to identify potential targets that
could be predictive and/or indicative of the development and severity of the disease. As it
is well-established that COPD and lung cancer commonly coexist in smokers, and the
presence of COPD increases the risk of developing lung cancer, we will also investigate
changes in COPD relating to increased susceptibility to lung cancer.
Mobile health for COPD – Prof Ian Yang
Clinical guidelines for chronic obstructive pulmonary disease (COPD) are available for use
by clinicians; however, the dissemination of these, despite systematic efforts, is still
suboptimal. Similarly, educational resources for patients with COPD are widely available
in hard copy and online; however, patients do not always access these appropriately in a
timely manner. This project will address these gaps, by using mobile technologies to
deliver medical management tools to clinicians, and self-management tools to patients, for
enhanced management of COPD. The expected outcomes of this study will be enhanced
uptake of COPD guidelines by clinicians, and improved self-management of COPD by
patients, through application of mobile health technologies.
Characterisation of Mesothelioma Cell Lines – Assoc/Prof Rayleen Bowman
Mesothelioma is a deadly asbestos related cancer that may develop many years after the
exposure to even a small amount of asbestos. There is no known cure but chemotherapy
may prolong survival in patients who respond. Australia has the highest incidence of
mesothelioma per capita in the developed world, and a strong track record in
mesothelioma research. To sustain international research competitiveness and capitalize
on emerging technologies with potential to discover therapeutic targets for mesothelioma,
the 2011 NCARD meeting ratified the need for curated national tissue banks and cell line
repositories to facilitate mesothelioma research. This project aims to establish a fully
annotated tissue bank and genomic DNA source, and a fully characterized mesothelioma
cell line repository.
Whole Genome Sequencing of Mesothelioma – Assoc/Prof Rayleen Bowman
Mesothelioma is a deadly asbestos related cancer that may develop many years after the
exposure to even a small amount of asbestos. There is no known cure but chemotherapy
may prolong survival in patients who respond. Whole genome sequencing has paved the
way for large-scale analyses of tumour biology. The project aims to sequence complete
genome of mesothelioma tumour samples and use this data to elucidate tumour biology
and identify novel candidate therapeutic targets. Firstly; the cell lines (cultured from the
biopsy / pleural fluid samples from patients) will be characterized and the second part will
include sequencing of whole genome to reveal the deeper complexity of the disease. That
will lead to identification of key dysregulated pathways, which can better inform prognosis,
and enable targeting of therapies to improve outcomes.
Anti-cancer Activity of Candidate Drugs for Mesothelioma – Assoc/Prof Rayleen
Bowman
Malignant Mesothelioma (MM) is an aggressive pleural malignancy caused by asbestos. It
will be a major health threat for many years to come, but peak incidence in Australia is
occurring this decade. Current treatments are of limited effectiveness with few active
chemotherapy agents available. For the last two years we have been involved in
discovering compounds with activity against mesothelioma by screening mesothelioma
cell lines with the John Hopkins Clinical Compound Library (JHCCL) (>1500 approved
drugs). After a pharmacotoxicology literature search, we have short listed 8 antimesothelioma compounds and now aim to confirm the activity of these drugs in
mesothelioma cells derived from an independent set of individuals. Drugs with confirmed
anti-mesothelioma activity can then be tested in clinical trials. If successful, this approach
may result in new and more effective treatment for patients with mesothelioma.
Breath Testing to Detect Lung Diseases – Dr Annette Dent
Breath testing is a simple minimally invasive method of collecting exhaled breath samples
(volatile organic compounds – VOCs and exhaled breath condensate - EBC). These
specimens may have diagnostic utility for lung disease including lung cancer. This project
will evaluate the potential of testing biomarkers in exhaled breath for the purposes of
diagnosing lung diseases.