Translational Oncology Research Group
DCIS (Ductal carcinoma in situ)
Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of non-invasive neoplastic lesions, comprising malignant-appearing epithelial cells, confined to the breast terminal duct lobular units that differ in histologic appearance and biological potential. While little is known about the natural history of DCIS, it is widely considered to be a precursor in the evolution of invasive breast cancer.
Our current project involves sequencing a large cohort of DCIS tumours with the aim of identifying and validating novel biomarkers with prognostic power in DCIS. There is a clinical need to develop and validate new biomarkers to improve risk assessment and treatment decision-making for women with DCIS. Reliable and accurate identification of women with a high risk of recurrence will allow for more effective use of adjuvant systemic therapies such as endocrine therapy and HER2-targeted therapy and even selection of some patients for mastectomy rather than BCS. This will also spare patients who are unlikely to recur from unnecessary over-treatment.
Radiotherapy - ImpactBio Project
Radiotherapy is an important part of the multimodality treatment for breast and other cancers and plays a vital role in maximising local disease control, enabling safe breast conservation and contributing to increased survival rates. The major setting for radiotherapy is after surgery as part of adjuvant treatment and is often followed by a boost dose for high risk patients. Loco-regional radiotherapy is also given as palliative treatment to relieve distressing symptoms (pain, discharge) and improve quality of life.
In collaboration with the EPSRC funded IMPACT project (www.impact.eng.ed.ac.uk), which aims to develop an implantable biosensor to monitor response to radiotherapy in real time, we have focused on the identification of secreted biomarkers of radiotherapy response. We develop radio-resistant models and carried out a series of high-throughput genomic and proteomic experiments to identify novel tumour-secreted biomarkers of radiotherapy response. Current work is focused on validating these biomarkers in vitro, in large animal models and in breast cancer explants.
In collaboration with Dr Daniel Good and Professor Alan McNeill, our current study utilises sequencing of a large cohort of prostate tissues and is designed to investigate and characterise the molecular basis of elasticity in prostate cancer diagnosis as part of the “e-finger” mechanical diagnostic device development programme.
The temperature around a malignant tumour correlates with micro vessel density (MVD) – the main indicator of angiogenesis. The temperature of a malignant tumour is also an indicator of growth rate of that tumour and more malignant lesions have a higher MVD. Measuring the temperature of a cancer therefore has the potential to provide insight into the degree of malignancy. Early during treatment with chemo or hormonal therapy, proliferation and metabolic rate falls in responding cancers and this should be reflected by a fall in the tumour temperature.
A microwave radiometry device that non-invasively measures the temperature within a cancer has the potential benefit of providing information on tumour proliferation and metabolism and could be used as an early indicator of benefit to individual therapies and for monitoring efficacy of systemic breast cancer treatments. Our current project is a pilot study which will investigate the clinical application of a microwave radiometry device to breast cancer diagnosis and measurement of treatment response.
In Situ Mutation Detection
Approximately 70% of breast cancers are estrogen receptor positive (ER+). Not all ER+ cancers respond to endocrine therapy and many eventually develop acquired resistance. Next-generation sequencing (NGS) has shown ESR1 mutations (ESRMs) are present in 10-50% of recurrent/metastatic cancers treated with aromatase inhibitors. Many of these mutations are located in the ligand-binding domain of ER, so they can lead to constitutive activation. This suggests ESRMs are a major mechanism of acquired resistance to endocrine therapy and numerous studies have shown a link between ESRMs and reduced sensitivity to 2nd line endocrine therapy. Our current project has focuses on the development and validation of a clinically-applicable in situ mutation detection approaches for the identification and quantitation of ESRMs and other mutations in patient cancer tissues.