Mini-tumors derived from circulating breast cancer cells offer new avenues for treatment strategies.

Using these mini-tumors, researchers were able to decipher the molecular signaling pathway that ensures the survival of cancer cells and their resistance to therapy. With this knowledge, the team developed an approach for the specific destruction of these tumor cells in laboratory conditions.

The results of the study were published in the journal Nature Cancer.

Metastases of breast cancer occur when cancer cells detach from the primary tumor and migrate to other organs through the bloodstream. These circulating tumor cells (CTCs) are extremely rare and are hidden among billions of blood cells. Andreas Trumpp, head of the research department at DKFZ and director of HI-STEM, demonstrated several years ago that only a few of the circulating tumor cells are capable of forming new metastases in another organ.

These therapy-resistant "embryonic" metastatic cells are rarely detected, are difficult to isolate, and have not yet been able to be cultured in the laboratory.

This complicates the development of targeted treatments that directly attack the cells initiating metastases. However, understanding how these cells survive after initial therapy and what causes their resistance could help to cut off the formation of breast cancer metastases at the root and possibly even prevent their occurrence in the future.

Trumpp's team was the first to successfully culture circulating tumor cells from blood samples of breast cancer patients and grow them as stable tumor organoids in culture media. Until now, this always required an indirect approach, namely the complex and lengthy cultivation of CTCs in immunodeficient mice. To understand how tumor cells become therapy-resistant, researchers need tumor material obtained at different time points during the disease progression. Unlike surgical removal of tissue samples (biopsies), blood samples can be easily taken and collected multiple times.

From blood samples, three-dimensional and patient-specific mini-tumors can be grown several times throughout the disease, making them ideal for studying the molecular mechanisms that allow tumors to survive despite therapy. Additionally, preclinical trials of the effectiveness of existing anti-tumor drugs can be quickly and extensively conducted on the organoids in culture media.

The ability to cultivate CTCs from the blood of breast cancer patients as tumor organoids in the laboratory at different time points is a revolutionary breakthrough. This significantly facilitates the study of how tumor cells become therapy-resistant. Based on this, new treatment methods can be developed that specifically target and destroy drug-resistant tumor cells.

Another possible approach is to adapt existing treatment methods in a way that reduces or even prevents the development of resistance and metastases from the very beginning. Since the organoids are specific to each patient, this method is suitable for identifying or developing individualized treatment methods that optimally match the respective diseases.