An ambitious project from the Garvan Institute of Medical Research will shine a spotlight on the complex molecular environment of breast cancers, providing unprecedented insights into the disease and, potentially, help develop better treatments.
The ‘Breast Cancer Cell Atlas’ will catalogue data from a million individual cells from patient breast tumours, collected over the past five years – the most comprehensive view of breast cancer yet.
The project will complement the Human Cell Atlas project, a global initiative aiming to map every single cell in the healthy human body, which could have a significant impact on our understanding of disease. It will be the first ‘Atlas’ project to be undertaken in collaboration with the Garvan-Weizmann Centre for Cellular Genomics.
The breast cancer ecosystem
A breast tumour is not just a cluster of one type of cancer cell – it is a complex mixture of many different cancer cell types, connective tissues and immune cells, says Associate Professor Swarbrick, who heads the Tumour Progression Laboratory at Garvan and leads this project.
“The different cells within a tumour act as an ecosystem – and these cellular interactions play a big role in defining a patient’s health and disease trajectory. We also think new drug targets will be found within this ecosystem,”explains Associate Professor Swarbrick.
“However, current methods to study a patient’s breast cancer often rely on ‘blunt’ tools, such as measuring the shape or number of certain cell types in a tumour,” he adds. “It’s like staring at something from a thousand miles away and trying to make out important details.”
“Thanks to cutting-edge cellular genomics technologies, Garvan researchers have new tools to investigate the cellular and genetic makeup of tissues at resolution of single cells, instead of studying the ‘blurry’ average of millions of cells. Associate Professor Swarbrick’s team will use these tools to understand the cellular and molecular details of breast cancers – and then to relate these discoveries to clinical features and the behaviours of those cancers.
The team’s objective is to find new drug targets for breast cancers by identifying the molecular features that consistently associate with patients that have poor clinical outcomes, and to develop therapeutic strategies to target them.
“We wouldn’t be able to create the Breast Cancer Cell Atlas without the contributions and commitment from patients who donate tissue samples for research. Thanks to the right technology, we will now be able to understand all the forms that the breast cancer ecosystem can take and the individual cells involved,” says Associate Professor Elgene Lim, who heads the Connie Johnson Breast Cancer Research Laboratory at Garvan. “This approach will provide us with a completely new way to look at breast cancer.”
Over the past five years, a team of clinicians and scientists led by Associate Professor Swarbrick, Associate Professor Lim, Professor Sandra O’Toole (Group Leader, Translational Breast Cancer Research) and Associate Professor Joseph Powell (Head of the Garvan-Weizmann Centre for Cellular Genomics) has been collecting samples from over 200 breast cancers, preparing them for cellular genomic analysis.
To do this, the team developed a customised method for storing the samples, preserving them in a more gentle way, to be compatible with cellular genomic sequencing platforms at the Garvan-Weizmann Centre for Cellular Genomics.
Now, the researchers will measure the levels of more than 20,000 genes and more than 150 proteins from around 5,000 cells per sample – preparing an ambitious Breast Cancer Cell Atlas that consists of comprehensive genomic and protein measurements of a million cells.
Using their cellular genomics approaches, the scientists have already made new discoveries about breast cancers, including that white blood cells, deployed from the lymph nodes, can mount a type of immune response within a breast tumour.
Combining this new information with years of clinical data collected for each patient will provide an unprecedented look into breast cancer biology, says Associate Professor Swarbrick.
“This project has been many years in planning, but thanks to the development of the Garvan-Weizmann Center for Cellular Genomics, it is now possible to complete,” says Associate Professor Swarbrick. “You can’t do these ambitious projects in a lab – they’re only possible with genomic capabilities such as those available at Garvan.”
The team is also planning a second phase of the Breast Cancer Cell Atlas Project by integrating their genomics capabilities with new methods to visualise the precise location of cells, and the genes and proteins they produce, within the three-dimensional space of a tumour. This will advance the researchers’ ability to understand the important interactions between cells.
“We’ll have a rich dataset of high quality molecular and cellular data that will be multi-dimensional because of the technologies we’ve got in the building,” says Associate Professor Swarbrick. “We are leading in the application of single cell genomics to oncology.”
The first phase of the Breast Cancer Cell Atlas project is one of six Garvan research projects funded by the National Breast Cancer Foundation.