Cell culture platform recreates tumours in 3D

Why doesn’t the same treatment work in the same way for every cancer patient? How can a drug’s performance be optimised without causing side effects due to an excessive dose? In an attempt to answer these questions, researchers at the University of Geneva (UNIGE) have devised a cell co-culture platform that reproduces a patient's tumour structure in 3D.

The scientists can use the 3D structure to test several drugs or their combinations at different stages of the tumour’s development. They now need only five days to identify which treatment will be most effective for a particular case, and the combination can then be translated for clinical practice. Their work has been published in the journal Scientific Reports.

Colorectal cancer is the third most common form of cancer diagnosed today and the fourth most deadly in the world. A range of treatments is available, but the high doses cause numerous side effects and patients commonly develop resistance. These treatments are currently tested on 2D tumour cell cultures before being administered to patients.

“But that doesn’t correspond to reality,” said Professor Patrycja Nowak-Sliwinska from UNIGE’s Faculty of Science. “Not only does a tumour develop in 3D, but it also contains other types of cells, such as fibroblasts (tissues) and endothelial cells (blood vessels).”

As a result, the Swiss scientists have built a new platform that uses a patient’s tumour cell lines to recreate the tumour in 3D. The platform keeps the tumour alive so that the impact of the treatments can be analysed during the different stages of its development.

Headed by Prof Nowak-Sliwinska, the team selected six cell lines derived from six different patients. The cells were stabilised in a hollow, U-shaped culture plate so that they stayed agglomerated and floated in a cell culture medium optimised to feed the tumour.

“The structure can then be organised by itself in 3D and continue its development,” said Prof Nowak-Sliwinska. “The three types of cells that make up the tumour carry on interacting with each other, as though they were in the patient’s body.”

The researchers then tested several different combinations of three approved drugs at different developmental stages of the cultured tumours. As noted by Prof Nowak-Sliwinska, “Our first observation was that each patient responded differently to the same combination, demonstrating that it’s impossible to reach similar efficacy for each patient with the same treatment. It needs to be considered on a case-by-case basis.”

The scientists also found that a low-dose combination of three drugs was much more effective than a high dose of one drug alone. Prof Nowak-Sliwinska explained, “Treatment resistance and side effects occur when the dose is too high. Combining several drugs at low doses helps to circumvent this problem and improve treatment responses.”

The new platform thus opens the door to personalised medicine, with Prof Nowak-Sliwinska noting how different drug combinations can be tested directly on a specific tumour and the optimal treatment selected for that particular patient. This meticulous work takes five days on average, a short enough time to act quickly against the cancer.

“In this instance we’re interested in colorectal cancer but this platform, which is easy to reproduce, can obviously be used for all kinds of tumours at a relatively low cost,” Prof Nowak-Sliwinska said.

Image caption: Representative image of a 3D model of colorectal carcinoma (HCT116 cells) exposed for 72 hours to treatment with a three-drug combination containing regorafenib, erlotinib and 5-fluorouracil. The cell-tracker stained cells correspond to cell nuclei (blue), live cells (green) and dead cells (red). Image© UNIGE, Molecular Pharmacology Group.

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