Centre for Dynamic Imaging

Single cell imaging techniques are allowing researchers, including Dr Kim Pham, to develop complex mathematical models to understand how cancer cells respond to chemotherapy.

In recent years chemotherapy has dramatically improved outcomes for patients with blood cell cancers. When successful, chemotherapy kills cancer cells with minimal damage to surrounding healthy cells. However in some cases the treatment has too many toxic side effects, or too little effect at all.

Single cell imaging techniques are allowing researchers to develop complex mathematical models to understand the rules that regulate how cancer cells respond to chemotherapy.

These models can be used for rapid evaluation for better chemotherapeutic treatments for patients.

Finding the right combination is a key step towards personalised chemotherapies

Dr Kim Pham, a postdoctoral researcher in the Hodgkin laboratory, performs single cell imaging to track cancer cell behaviour in fine detail. When she adds a chemotherapy drug to a population of cancer cells, she can watch what happens to each individual cell over a period of time.

Single and combined chemotherapeutic drugs have become essential to treat a wide range of blood cancers. Despite mounting effort directed toward personalised chemotherapies, it has been impossible to explore the huge number of possible chemotherapeutic combinations to tailor treatments for patients.

We also have little understanding of why certain combinations are effective.

Mathematical models explain differences in chemotherapy response

Dr Pham and her colleagues use mathematical models to understand variation in cell fate behaviour. The models describe how cells decide whether to divide or to die, and help explain differences in behaviour among similar cells. Initially developed in healthy immune cells, the models apply equally to cancer biology and can be used to predict the effects of chemotherapy.

Advanced imaging techniques fine-tune mathematical models

Dr Pham and her colleagues use technology platforms at the Institute to fine-tune their models and test their predictions. Techniques like flow cytometry provide some information about what happens when cancer cells are treated with chemotherapy drugs, but the information is only a snapshot of what the entire population of cells is doing at one particular time.

At the Centre for Dynamic Imaging, Dr Pham performs single cell imaging to track cancer cell behaviour in fine detail. Using the Zeiss Axio Observer microscope she can observe what occurs when a chemotherapy drug is added to a population of cancer cells. The technique also allows her to watch what happens to each individual cell over a period of time. Staff at the Centre assist Dr Pham with image analysis, resulting in a rich data set to inform Dr Pham’s models of how chemotherapies work from a single cell to the whole population level.

Applying models to improve cancer care

Dr Pham can now apply her cancer cell models to:

• Better understand single and combined chemotherapies in blood cancers
• Predict effective chemotherapy drug combinations for blood cancers
• Examine the evolution of cancer cells