Kinase Biomarkers Are Active in Basal Breast Cancer

A protein screening technology has been used to profile basal breast cancer, a particularly aggressive sub-type of breast cancer, identifying specific targets for future treatments.

Basal breast cancers display a characteristic "signature” or "fingerprint” of tyrosine phosphorylation, or phosphate molecules attaching to the tyrosine amino acids within proteins. These characteristics can be ascertained by various methods including Phosphopeptide immunoprecipitation, phosphorylation assays with tyrosine kinase inhibitors, and cellular proliferation assays.

Scientists at the Garvan Institute of Medical Research (Sydney, Australia), subjected cancer cells to mass spectrometry-based profiling of protein tyrosine phosphorylation events. They have focused in particular on a process known as phosphorylation, a way in which proteins modify each other's behavior by exchanging phosphate molecules. In addition, rather than looking at proteins one at a time, they have used a technology that allows the investigator to examine the phosphorylation of all cellular proteins.

Their findings show that basal breast cancers display a tyrosine phosphorylation signature and these cancers show heightened activity of several different kinds of cell-signaling proteins known as kinases. Kinases are responsible for attaching the phosphate groups to proteins. Each cancer type has a submicroscopic fingerprint defined by its proteins and until now, basal breast cancer's protein fingerprint had remained elusive. These studies highlight multiple kinases and substrates for further evaluation as therapeutic targets and biomarkers. However, they also indicate that patient stratification based on expression/activation of drug targets, coupled with use of multi-kinase inhibitors or combination therapies may be required for effective treatment of this breast cancer subgroup. Basal breast cancers represent between 10 and 27% of all breast cancers, depending on the population sampled. They lack estrogen 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.

Falko Hochgräfe, Ph.D., the senior author of the study, said, "Our findings suggest that it would be a good idea to stratify patients according to which signaling 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" The study was published online in October 2010, in Cancer Research.

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Garvan Institute of Medical Research