Tumour organoids from breast cancer patients successfully cultivated for the first time

Stable tumour organoids have been directly taken from blood samples of breast cancer patients; in a world first that could speed the development of new treatments

Tumour cells circulating in the blood are the “germ cells” of breast cancer metastases – cancer cells that detach from its original tumour and spread around the body. Until now, these cells could not be  propagated in culture dishes, posing a barrier to research into therapy resistance.

Using these mini-tumours, researchers have deciphered a molecular signalling pathway that ensures the cancer cells’ survival and resistance to therapy, enabling the development of an approach to eliminate them.

The researchers emphasise that these circulating cancer cells (CTCs) are extremely rare and hide among the billions of blood cells.

Andreas Trumpp, head of a research division at the German Cancer Research Center (DKFZ), which carried out the study, had previously shown that only a few CTCs can form a new metastasis in another organ.

Roberto Würth from Trumpp’s lab and first author of the paper said: “This makes it difficult to develop targeted new therapies that directly attack the metastasis-initiating cells. However, if we understand how these cells survive the initial therapy and what drives their resistance, we could tackle the formation of breast cancer metastases at the root and perhaps one day even prevent them.”

The researchers were able to multiply the CTCs and grow them as stable tumour organoids in the culture dish.

The team say that three-dimensional and patient-specific mini-tumours can be cultivated from blood samples several times during the course of the disease and are ideally suited for investigating the molecular mechanisms that enable tumours to survive despite therapy.

They found that the protein NRG1 acts like a fuel, binding to the HER3 receptor on the cancer cells and, together with the HER2 receptor, activates signalling pathways that ensure the growth and survival of the cells, and that an alternative signalling pathway, controlled by FGFR1, ensures growth and survival.

“With the help of such ‘bypasses’, tumours react to external influences, for example to targeted therapies against HER2. This is a crucial mechanism in the development of therapy resistance,” said Würth.

The researchers then used organoids to show that blocking both the NRG1-HER2/3 and FGFR signalling pathways can effectively stop the tumour growth and induce cell death.

Trumpp said: “The possibility of cultivating CTCs from the blood of breast cancer patients as tumour organoids in the laboratory at different time points is a decisive breakthrough. This makes it much easier to investigate how tumour cells become resistant to therapies.

“On this basis, we can develop new treatments that may also specifically kill resistant tumour cells. Another conceivable approach is to adapt existing therapies in such a way that the development of resistance and metastases is reduced or even prevented from the outset.

“As the organoids are specific to each patient, this method is suitable for identifying or developing customised therapies that are optimally tailored to the respective diseases.”

The team say the method must now be tested in clinical trials.