Why we focus on Cancer, Stem Cells and Ageing
Stem Cells & Cancer
With the availability of ever more sophisticated model systems and technologies it has now become evident that cancers are driven by phenotypic and functional heterogeneity and that striking plasticity exists within each subclone. So-called cancer stem cells are responsible for this intraclonal heterogeneity (Figure 1).
Cancer stem cells represent a subset of cancer cells, for which we and other have provided conclusive evidence down to the single-cell level that they represent the root of the disease by giving rise to all differentiated progenies within each cancer subclone. Even more importantly, these cells are driving the metastatic behaviour of many cancers and represent an important source for disease relapse. Thus, cancer stem cells should signify a crucial component for any novel treatment approach.
|Figure 1 – Cancer stem cell concept and cancer evolution|
Cancer & Ageing
In the UK, 155,000 people aged 70+ years are diagnosed with cancer every year representing 50% of all cancer diagnoses, a number likely to rise as the population ages. Survival rates for older cancer patients lag behind younger patients with the same cancers. We now face new problems in understanding the biology of older people who develop cancer, which also includes, but is not limited to important co-morbidities such as diabetes and metabolic syndrome.
Compelling new evidence from the Barts Cancer Institute (BCI) indicates that epigenetic controls are fundamental to many molecular switches between senescence and immortalization. Furthermore, DNA methylation is a central mechanism underpinning genome stability and gene expression. Many other hallmarks of ageing have also been implicated as also important determinants of cancer initiation and/or progression (Figure 2). Therefore, cancer needs to be studied in the appropriate context, but most of our current cancer models are lacking important aspects of ageing, co-morbidities and subsequent changes to the tumour microenvironment.
Figure 2 – The Hallmarks of Ageing (modified from Lopez-Otin et al. Cell 2013)
What we do
The BCI will pioneer a Centre for Cancer, Stem Cells & Ageing that spans both molecular and patient biology to address the twin issues of cancer and ageing in cancer (stem) cells and in people. Building on our established strength in stem cell biology, we will further expand our laboratory programme to important aspects of our ageing patient population including age-related co-morbidities.
Our programme will join efforts with established research strands at BCI focusing on DNA repair and genome stability, epigenetics and senescence, as well as ageing and immune function. In collaboration with our Clinical Trial partners at Brighton and Sussex Medical School, who have an established a clinical research programme in older patients with cancer, and with Attilla Lorincz (Molecular Epidemiology, Wolfson Institute of Preventive Medicine), we are in a position to apply newly developed quantitative tools for DNA methylation analyses, such as pyrosequencing and deep sequencing of methylomes, coupled with bioinformatics to determine the levels of tissue genome plasticity and the role of driver epigenetic mutations in diverse cancers.