Taking the fingerprint of basal breast cancer
Basal breast cancers represent between 10 and 27% of all breast cancers, depending on the population sampled. They lack oestrogen and progesterone receptors, so are resistant to hormone therapies such as tamoxifen. They are also resistant to Herceptin, a monoclonal antibody effective in treating a different subset of breast cancers.
As a result, the dilemma for clinicians is that there is no effective ‘targetted’ therapy for basal breast cancer.
The main reason for this absence of knowledge is that cancers behave in extraordinarily complex ways, well below the cellular level. Each cancer type has a submicroscopic fingerprint defined by its proteins – the molecules that carry out work in cells. Until now, basal breast cancer’s protein fingerprint has remained elusive.
Every cell in our body contains thousands of proteins, each with a specific function. They interact continuously, usually by changing each other biochemically. When cells are normal, they contain predictable levels of specific proteins, talking to each other in predictable ways. When cells are cancerous, protein levels change and so do the ways in which they communicate.
Dr Falko Hochgräfe and Professor Roger Daly from Sydney’s Garvan Institute of Medical Research, have spent the last two years examining protein behaviour in basal breast cancer. They have focused in particular on a process known as phosphorylation, a way in which proteins modify each other’s behaviour by exchanging phosphate molecules. In addition, rather than looking at proteins one at a time, they have used a new technology that allows the investigator to examine the phosphorylation of all cellular proteins.
Their findings show that basal breast cancers display a characteristic ‘signature’ or ‘fingerprint’ of ‘tyrosine phosphorylation’, or phosphate molecules attaching to the tyrosine amino acids within proteins. In addition, these cancers show heightened activity of several different kinds of cell-signalling proteins known as ‘kinases’. Kinases are responsible for attaching the phosphate groups to proteins.
These findings are described in the prestigious international journal, Cancer Research, now online.
“We were able to outline the signalling network which is characteristic for basal breast cancers, and identify which kinases are present and active,” said Hochgräfe.
“Our findings suggest that it would be a good idea to stratify patients according to which signalling proteins, or kinases, were found in their cancers. These kinases can then be targeted by specific therapies – and because several kinases are commonly activated in basal breast cancers, use of combination therapies that target more than one kinase, or multi-kinase inhibitors, is likely to more effective in the clinic.”
“As well as mapping out signalling networks, we also found a couple of novel markers – proteins which could potentially be used to identify this patient subset, and which might help create a more tailored therapy in the future.”
The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with nearly 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.
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