A tumour-on-a-chip system could make investigating potential anti-cancer drugs easier and more reliable while reducing the need for testing on animals. The device uses model tumour ‘spheroids’ sustained by a network of blood vessels. It also offers an improved method for investigating cancer growth in general and exploring the problematic emergence of drug resistance.

Researchers in Japan led by Ryuji Yokokawa at Kyoto University report the development of the technology in the journal Biomaterials.

The ability to mimic blood flow through a tumour is the key advantage of the new procedure. Other researchers have grown model tumour-on-chip systems, including some that developed blood vessels, but they could not recreate the blood flow that sustains the unique micro-environment nourishing a tumour. Those previous attempts had often led to blood vessels that were blocked by dead ends.

Lab-grown mini-tumours with a network of functioning blood vessels will assist understanding of cancer and drug testing
Lab-grown mini-tumours with a network of functioning blood vessels will assist understanding of cancer and drug testing

The team in Japan managed to find culture conditions that allowed spheroids of human breast cancer cells to build working blood vessels. The researchers were assisted in this achievement by lessons learned in previous work they had done with cultured human lung cells. They were able to observe new blood vessels sprouting from precursor cells, in the process called angiogenesis which is essential to maintain a rich blood supply for a growing tumour.

“It has been difficult to study the effect of blood flow in animal models due to the limited access to the blood vessels,” says Yokokawa, explaining why achieving working blood vessels has been such an important target. He also explains that the new device gives the researchers precise control over the nutrients and other chemicals that are flowing through a tumour. “The effects can all be studied biochemically and under a microscope in real time,” he adds.

The new device has already allowed the researchers to explore the difference between the effects of varying flow rates and different doses of therapeutic drugs. These issues, while critical, remain unclear. The new ability to examine them in human cells under more readily controlled conditions should help bring more clarity and precision.

“Some of our findings have been surprising and counter-intuitive,” Yokokawa says. For example, studies of cultured tumours with no blood supply reveal a direct dependence of the anti-cancer effect on the administered dose. In the more realistic situation with mimicked blood flow, such direct dose-dependence was replaced by more complex relationships between flow-rate, dose, and effect.

The studies also confirmed and helped quantify the positive effect that a realistically modelled flow of nutrients has on the survival and proliferation of the tumour cells.

The researchers now plan to widen their technique to grow other types of cancers to greatly increase the applicability of the technique, perhaps including other diseases in addition to cancer.

“We hope to build a new and versatile drug screening platform,” Yokokawa concludes.

Any reduction in animal testing will also be welcomed by those campaigning against the use of laboratory animals in science while also questioning the relevance of animal tests to the human situation.

Article details: 

Yokokawa, R. et al.: “Vascularized cancer on a chip: The effect of perfusion on growth and drug delivery of tumor spheroid,” Biomaterials (2020).