Recently, we asked several of Canada’s leading stem cell scientists to tell us about what they think will be the next big thing in regenerative medicine. Where do they see things going? What are they excited about? For today’s instalment, we interviewed Dr. Connie J. Eaves is a Distinguished Scientist at Vancouver’s Terry Fox Laboratory, which she co-founded. A Professor of Medical Genetics at the University of British Columbia, she is world-renowned for her pioneering research in basic blood stem cell biology, which led to new treatments for leukemia. She also isolated breast stem cells and is a leading thinker in the field of breast cancer. Here’s what she’s excited about in 2015.
I was a co-author of a Nature paper in December that was led by Drs. Samuel Aparcio and Sohrab Shah (University of British Columbia) and described the changing genomic composition of breast cancer xenografts — that is fragments of patients’ breast tumours growing in special transplanted mice that have no immune system. In such mice, many patients’ tumours can grow as if they were still in the patient. You can thus track how the tumour evolves in relation to the original tumour.
This model has significant implications for developing new ways to treat cancer, because you can use the tumours created in the mice to determine which treatments work best and how that compares to the mutations that were present in cells that disappeared and those that may be unique to the cells that proved resistant. Groups all over the world are trying to use this approach, so we’re excited about that.
My lab has another paper in the works that has to do with making human breast tumours starting with normal human breast tissue. We have developed a protocol in which normally discarded breast tissue samples obtained from women undergoing cosmetic surgery are infected with a mutant cancer-causing gene and then produce tumours when transplanted into immunodeficient mice.
The reason this is extraordinarily exciting is because people have been trying to do this this for years with blood cells and it’s been difficult: you can count on one hand the number of different mutant genes (out of many tried) that can produce a leukemia when put into normal human blood-forming cells. Indeed, this has been very discouraging in the leukemia field.
The idea is, if you could study the early events that cause leukemia or breast cancer, then you would be able to look into the first changes that occur and get a handle on those. You could then look for those changes in a patient’s samples and try to target them specifically. Since they are the first events, they are likely going to be in every daughter tumour cell in that patient and hence better (more universal) targets.
One of the problems with treating many tumours is their genetic instability, which leads to the genesis of a tremendous diversity of subclones of cells carrying additional new mutations. Thus when you use a treatment strategy that can kill a dominant clone, there may be another 100 subclones that are not eliminated lurking at lower levels that then regrow. That is why the idea of understanding how a tumour starts to develop from its earliest stages is so captivating. Being able to do this with human breast tissue was unexpected and opens the door to all sorts of experiments. So we’re very excited about this new line of work.