While cancer is a common disease in humans, neoplastic change is very rare at the cellular level, with on average less than 10% of pre-neoplastic lesions progressing to malignancy. Currently, both the mechanisms that prevent neoplastic change and their breakdown during neoplastic progression are poorly understood. There is significant evidence demonstrating that heightened understanding of the early steps in carcinogenesis will lead to new approaches for early clinical intervention, with a potentially high impact on patient outcomes. Indeed, five-year survival for virtually all forms of cancer greatly improves if the disease can be treated at its early stages. Nevertheless, only a small proportion of cancer research currently focuses in this area.
The MRC Cancer Unit’s mission is to improve understanding of the earliest steps in epithelial carcinogenesis and to utilize this knowledge in new approaches for clinical intervention through the development of innovative enabling technologies. We believe that improved understanding of the earliest steps in the transformation of normal cells into cancers will lead to new methods to improve the care and survival of patients with common and serious malignancies such as oesophageal, skin, lung, kidney and pancreatic cancer. The Unit receives core funding from the Medical Research Council, with additional external support from the Wellcome Trust, CRUK and other sponsors. Research at the Unit is conducted in 10 faculty-led programmes and supported by approximately 140 staff.
Our work has three broad objectives:
- To advance scientific understanding of the earliest steps in the emergence of epithelial cancers during the transition from pre-neoplastic to invasive disease.
- To translate this understanding into early clinical interventions for diagnosis, risk stratification and treatment that improve patient outcome.
- To develop innovative, interdisciplinary technologies to underpin the delivery of these aims.
Our mission is unique within the MRC’s Unit portfolio for its focus on early steps in carcinogenesis, its close integration of laboratory research on disease mechanisms with translational and clinical activities for improved early diagnosis and therapy, and the multidisciplinary technological platforms we have developed for early detection, preclinical disease models, chemical biology, therapeutics, and systems microscopy.
Our research spans the following areas:
1) Tumour suppressor mechanisms in the control of genome stability and 2) Therapeutic target discovery and systems microscopy (with Grahame McKenzie and Alessandro Esposito) - led by Professor Ashok Venkitaraman
- Pathogenesis and therapy of BRCA2-deficient cancers
- DNA replication and repair mechanisms
- Chromosome segregation mechanisms
- Systems microscopy
- Chemical biology and molecular therapeutics initiative
Oesophago-gastric adenocarcinoma: understanding disease pathogenesis and applications to earlier diagnosis - led by Professor Rebecca Fitzgerald
- Development of a screening and treatment strategy for Barrett's oesophagus
- Understanding how Barrett's oesophagus develops into oesophageal adenocarcinoma and developing diagnostic tools to predict progression
- Clinical and molecular factors affecting the outcome of oesophageal adenocarcinoma to develop prognostic algorithms and novel therapeutics
Cell fate and cancer - led by Dr. Phil Jones (Joint faculty member with the Sanger Institute)
- Stem cell behaviour in the development of cancer
- Lineage tracing to track stem cells in vivo
Modelling tumour development and therapy - led by Dr. Carla Martins
- Mechanisms required for lung tumour evolution and maintenance
Stroma function in the tumour microenvironment - led by Dr. Jacqui Shields
Our interest in the function of supporting cells (stroma) within the evolving tumour microenvironment covers three main areas:
- Identifying the mechanisms of stromal-mediated immune dysfunction at the primary tumour
- Understanding how stromal cells operate in tumour draining lymph nodes, the first site of metastasis in many cancers
- Identifying mechanisms of resistance and novel therapeutic strategies to target the tumour stroma
Cancer Metabolism - led by Dr. Christian Frezza
- The role of altered metabolism in cancer, and understanding how metabolic transformation regulates the process of tumorigenesis
Molecular origins of metastatic cancer phenotypes - led by Dr. Sakari Vanharanta
- The role of early cancer mutations in metastatic cancer progression
- Mechanisms of oncogenic signal modulation in cancer progression
- Molecular dependencies of advanced cancer
Modelling the decision-making process of cancer - led by Dr. Benjamin Hall
- Building executable and hybrid/cyber-physical models of cell signaling processes, to understand how populations of cells in a tissue compete and develop in carcinogenesis
- Integrative computational approaches to understand multi-scaled biological systems involved in immunity, inflammation and cancer, and particularly the systems underlying tumerigenesis