Development of a novel lung-on-a-chip platform to investigate breast cancer metastasis

Breast cancer occurs due to changes in the breast tissue which allow cells to grow out of control.

Though breast cancer is one disease, it comes in different types and forms depending on where in the breast it starts and whether it is non-invasive or invasive. Cancer metastasis is the subsequent spread and invasion of the cancerous cells into other parts of the body beyond the breast tissue. The bones, lungs, brain, and liver are the most common places for breast cancer to spread to. Cancer spread is a leading cause of death in breast cancer patients.

Although our knowledge and treatment of breast cancer are improving, how breast cancer cells gain the ability to spread around the body is still not fully understood. To understand this better and identify the critical steps associated with breast cancer spread, we plan to develop a new laboratory model of breast cancer spread to the lung which will better imitate what occurs in the body when breast cancer spreads into healthy lung tissue. This will allow us to study the disease in detail and identify what factors help it spread.

At present, models that study the spread of breast cancer include animals that don’t faithfully represent the human disease or cells grown in petri-dishes in 2D which doesn’t reflect cells in the body in a 3D environment. As a result, these models are either too complex to unravel the step-bystep changes or limited by their lack of complexity. This project proposes to take advantage of recent advances made by organ-on-chip technology, which are devices that better mimic the working of the body (i.e., any organ in the body, for instance, the lungs including the mechanism of breathing and 3D environmental conditions).

We propose using this organ-on-a-chip platform to create a lung-on-a-chip that will help us better understand the cause of breast cancer spread into the lung tissue. Lung-on-a-chips are translucent devices that provide a window into the inner workings (i.e., the lung tissue composition, mechanical stretching imitating breathing, and flow rate imitating blood flow speeds) of the human lung without having to invade a living body. It has the potential to be a valuable tool for testing the effects of environmental toxins, absorption of inhaled therapeutics, and the safety and efficacy of new drugs. Such a tool may help accelerate drug development by reducing the reliance on current models.

The ability to recreate realistically both the mechanical and biological sides of the in vivo coin is an exciting innovation. Adopting this platform for modelling cancer metastasis will lead us a step closer to a greater insight into how this disease works. This is important because patients experiencing breast cancer spread have few treatment options. Therefore, by developing a more realistic cancer model we will learn more about why breast cancer spreads to the lung in addition to other sites, and potential new ways to treat it. These models are a promising tool for drug screening in both drug development and personal drug administration for NHS patients.