The further we delve into the molecular understanding of breast cancer, the more, we realise, there is still to find out. The key to finding this out is research.

Tuesday 26 August 2014      Research blog
Complex cancer

Complexity is everywhere. The vastness of space. Global economics. Navigating London bus routes. All incredibly complex. Science too can be extremely complex. The more we learn about something, the more questions we have to ask, leaving us perpetually filling an infinitely empty void with knowledge. This is called the ‘theory of ignorance’ as explained by French mathematician, Blaise Pascal:

“Knowledge is like a sphere, the greater its volume, the larger its contact with the unknown”.

Pascal’s idea resonates strongly with our knowledge of cancer. The further we delve into the molecular understanding of the disease, the more, we realise, there is still to find out.

Understanding resistance

One of the great problems with treatment for diseases such as breast cancer is that not all patients respond to treatments in the same way. We’ve developed some extremely useful drugs such as tamoxifen and Herceptin, which have been hugely successful for the treatment of ER and HER2 positive breast cancers, respectively. However, many patients with these types of breast cancer are either resistant to treatment or develop resistance during treatment.

Research has shown us that this resistance is likely to be caused, in part, by what scientists call ‘heterogeneity’. This is the notion that tumours are not made up of cancer cells which are all genetically identical but actually contain pockets, or compartments, of cancer cells with different genetic backgrounds.

These different cancer cells may have emerged from the same starting cell but have over time ‘evolved’ along distinct genetic routes. It’s a bit like looking up your old school friends on Facebook; you all started at the same school but your lives and jobs are now incredibly diverse. These differences were driven by events in each person’s life in the same way as molecular events have influenced the diversity of cancer cells within a tumour.

Heterogeneity makes tumours extremely complex. Breast cancer patients are stratified based on the genetic and molecular characteristics of their tumour, and it’s this stratification which helps determine the best choice of treatment. For example, a patient stratified as being ER-positive will likely receive tamoxifen after surgery to remove the tumour. This will help clear up any cancer cells left behind and prevent the disease coming back. The heterogeneity of tumours means that there could be some cells left behind which can’t be killed by tamoxifen because they have a genetic background making them resistant.

The next level

A paper published recently in Nature revealed that genetic diversity within breast tumours may be even more complex than originally thought. Using a revolutionary new method of sequencing, the researchers were able to isolate and sequence the genome of individual cancer cells within a tumour and compare them to the genetics of the general population of cancer cells making up the tumour.

Amazingly, the researchers found that not only were the genetic background of individual cells different from the population, but also each individual cell was genetically different from each other. This is heterogeneity on an unprecedented level and raises new questions about treatment resistance, tumour development and disease progression.

This research does carry good news though. The powerful tool they have developed for sequencing single tumour cells could be used to study the genetics of individual tumour cells present in a patient’s blood stream – helping to characterise the heterogeneity of a patient’s cancer and potentially leading to better ways of treating the disease.

Up to the challenge

Understanding heterogeneity to improve breast cancer treatment is a core piece of Breakthrough’s research. Our scientists are trying to develop new ways to identify how tumour vary genetically and use this information to ensure patients receive the most effective treatment for their diagnosis. We are also funding work to find out how, on a genetic and molecular level, secondary tumours differ depending on what organ they develop in and how they differ from the primary tumour.

Reading Pascal’s quote again, it does seem that the quest for knowledge is futile. But I believe his words hide a key fact. As problems are solved, yes, we create more questions. But we have also solved the initial problem, and that in itself is a triumph.  In breast cancer research this progression has led to major advances, which has seen the 10 year survival rates for breast cancer reach 77 percent. Something we owe to those dedicating themselves to filling and expanding the sphere of knowledge.

Dr Matthew Lam is Breakthrough Breast Cancer’s Senior Research Officer