A brain tumor of the Petri dish

Researchers at the IMBA – Molecular Biotechnology Institute of the Austrian Academy of Sciences – develop a new organoid for cancer research

Vienna (OTS) – Brain tumors are among the most aggressive cancers. Especially among young people, they are among the most common tumor diseases. Glioblastoma is particularly feared, characterized by very rapid tumor growth and particularly difficult to treat. It is now known that brain tumors are triggered by a variety of mutations in combination with external factors. In recent years, huge cancer genome sequencing projects have identified thousands of mutations found in patients' tumors. After all, it is mutations that determine whether healthy cells eventually turn into cancer cells that eventually proliferate, displace healthy tissue, and spread systemically. To date, scientists lacked a suitable model to study the effect of these mutations in the human brain.

The brain organoids developed at IMBA could now play a key role in cancer research. The research group around Jürgen Knoblich has recently developed a new model system for brain tumors. The novelty: The new technology allows researchers to replicate the process of carcinogenesis in the brain in the petri dish. The researchers are thus able to observe concretely how the organoid develops a tumor.

New model system of cancer research

In a publication in the latest issue of the journal Nature Methods, the research group reports the new neoplastic brain organoids they developed to study brain tumors. "These tiny organelles faithfully reproduce unique aspects of the human brain, such as its different cell types and developmental stages, allowing us to understand the development of tumors and provide a system for testing new therapies." said Jürgen Knoblich, Acting Scientific Director at IMBA and final author of the study.

Mutations are genetic defects caused by natural defects in the copy of DNA or by the activity of cancerous genes. This makes them unable to control and share incredibly fast, but whenever a cell divides, it can create new mutations, which is a mystery to scientists. "Some of these mutations are driving forces in tumors, they decide if cancer will arise," says Shan Bian, lead author of the study, "Others are simply side effects. Targeting these different mutations in human tissue has been a problem to date. "

Mapping Mutations and Testing Drugs

Newly developed neoplastic organoids offer incredible potential to systematically solve these problems through modern genome editing systems: CRISPR / Cas9 and the so-called Sleeper Beauty Transposons are used to introduce into cells mutations that are commonly found in cancer patients, allowing them to alter individual genes or gene combinations, disabling certain genes while increasing the activity of other genes The researchers want to distinguish between carcinogenic mutations and less serious mutations, and once a tumor has developed, scientists can examine specific mutations to determine if the particular genetic defect is also responsible for the long-term survival of the tumor.or is essential.All genetic modification which shrinks or disappears the tumor could be a good candidate for future therapies

Organoids for Personalized Cancer Medicine

Scientists have tested this principle with a drug called afatinib which is currently used in clinical trials for the treatment of glioblastomas. They found that after 40 days of drug administration, the number of tumor cells decreased significantly in both mutation combinations in which a molecule called EGFR is overexpressed – because afatinib inhibits l & # 39; EGFR. The researchers repeated the experiment with four additional drugs that inhibit EGFR and are currently used in therapies. While a drug called erlotinib significantly reduced the number of tumor cells, the effects of other drugs were minimal.

"These results indicate that brain organoids also have significant benefits for cancer research and public health, especially since it is now possible to produce organoids of patients with brain tumors and test the effectiveness of various therapeutic combinations, "says Jürgen Knoblich." Now this would be an important step to promote other clinical partnerships. We believe that our models could provide clues for the clinical management of brain tumors in the future. "

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Original Publication: Bian, et al., 2018, & quot; Genetically modified model of cerebral cerebral organoid & quot ;, Nature methods; doi : 10.1038 / s41592-018-0070-7 .

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