Researchers create models to study brain metastases that recapitulate disease

The spread of different types of cancer cells to the brain, forming brain metastases, is the leading cause of cancer-associated morbidity and mortality. Now a new study led by Cláudia C. Faria, principal investigator in the group of João Taborda Barata at the Instituto de Medicina Molecular João Lobo Antunes (iMM; Portugal) and neurosurgeon at Santa Maria Hospital (HSM, CHULN, Portugal ), and published today in the scientific journal Medicine Reports Unit created a library of models to study brain metastases that recapitulate disease in humans. These models can be a relevant tool for understanding the disease and discovering new therapeutic approaches adapted to each patient.

We collected brain metastases from cancer patients, originating from tumors located in different organs, and used these metastatic cells to generate disease models that mimic each patient’s disease, including the spread of cancer cells to form metastases. These unique and adapted models can now be used to study brain metastases and test new anti-cancer compounds. »


Cláudia C. Faria, first author and study leader, Instituto de Medicina Molecular

The mouse models were obtained from cells from samples of metastases from patients undergoing surgery at Santa Maria Hospital. “We created mouse models using brain tumor tissue directly from patients. These models function as a library that mimics the characteristics of each patient observed in the clinic. We can now return to this library to study cancerous brain metastases”, adds Rita Cascão. , also first author of the study.

Tumor models reflect the clinical manifestations of cancer in the patient. Cancer cells in these models spread to the same organs as in patients, and tumor formation is more efficient when using cells from patients with more aggressive disease. Besides similarities in the clinical development of tumors, the models also repeat the biological characteristics of the original tumor since the genes that are active in cancer cells in mice are similar to those that are active in patients. These tools can be valuable for personalized medicine, to decipher the best clinical approach to treat each patient. “The models we created in this study are like mirrors that recapitulate the disease in humans”, explains Cláudia C. Faria, and adds “like mirrors, the models can be used to carefully study the disease”.

In this study, researchers tested the ability of these models to serve as tools to assess the therapeutic value of different therapies. The team tested two known drugs that are already used as cancer treatments in the clinic and act on the processes involved in the formation of metastases. Similar to the clinic, these treatments are effective and reduce tumor growth and size in models. By testing these accepted treatments and showing their effectiveness, the researchers demonstrated the potential of the models to explore new therapeutic approaches for brain metastases in the future.

This work was developed at iMM in collaboration with the Neurosurgery Department and Neuropathology Laboratory of Santa Maria Hospital, Centro Hospitalar Universitário Lisboa Norte (Portugal), and with researchers from the European Institute of Bioinformatics, European Molecular Biology Laboratory (UK). This study was funded by the Portuguese Foundation for Science and Technology (FCT), the Millennium Foundation bcp and private donations.

Source:

Journal reference:

Faria, CC, et al. (2022) Patient-derived brain metastasis models recapitulate disseminated human disease. Medicine Reports Unit. doi.org/10.1016/j.xcrm.2022.100623.

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