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Researchers at the IMBA – Institute of Molecular Biotechnology of the Austrian Academy of Sciences – have developed a new organoid for cancer research
Vienna, 12 September 2015 – The Brain tumors are among the most aggressive and deadly. 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 for the first time at IMBA could now play a leading 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. As a result, researchers can virtually observe how the organoid develops a tumor.
Twelve: New Model of Cancer Research
In a publication of the latest issue of Nature Methods, the research group reports on the new "neoplastic brain organoids" that they developed for the first time. 39, study of 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, interim scientific director at IMBA and latest author of the study.
Mutations are genetic defects that are caused by natural defects in the copy of DNA or by the activity of cancer genes or that have other causes. In healthy cells, they trigger serious changes that make them uncontrollable and share them 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, "Other are side effects, targeting these different mutations." in human tissue has been a problem so far.
Twelve: Mapping Mutations and Testing Drugs
Newly developed neoplastic organoids offer incredible potential for systematically addressing these problems. Modern genome editing systems, such as CRISPR / Cas9 and what are called Sleeping Beauty transposons, bring into cells mutations that are commonly found in cancer patients. Thus, individual genes or gene combinations can be modified, some genes are disabled while the activity of other genes is increased, regardless of known genetic defects. The researchers want to distinguish between mutations causing cancer and less severe mutations. Once a tumor has developed, scientists can examine specific mutations to determine if the particular genetic defect is also essential for the long-term survival of the tumor. Because any genetic change that shrinks or shrinks the tumor may be a good candidate for future therapies.
Second: Organoids for Personalized Cancer Medicine
Researchers tested this principle with a drug called afatinib, which is currently used in clinical trials to treat glioblastoma. They found that after 40 days of drug administration, the number of tumor cells decreased significantly in these two mutant combinations in which a molecule called EGFR is overexpressed because afatinib inhibits it. ; 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 reduces the number of tumor cells, the effects of other drugs are minimal.
"These results show that brain organoids also have significant advantages for cancer research and public health, particularly because it is now possible to produce organelles in patients with brain tumors and test the effectiveness of different combinations of therapies, "says Jürgen Knoblich. "Now, this would be an important step in the pursuit of clinical partnerships, and we believe that our models could provide clues for the future of clinical brain tumor management."
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Original publication: Bian, et al., 2018, "The formation of brain tumors of the genetically modified organo-cerebral model", Nature Methods; doi: 10.1038 / s41592-018-0070-7.
Request for clarification: IMBA - Institute of Molecular Biotechnology GmbH Dr. Bohr-Gasse 3, 1030 Vienna H. :: +43 664 808 47 3628 [email protected] [email protected] Website: www.imba.oeaw.ac.at
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Original content by: IMBA Institute for Molecular Biotechnology, transmitted by news aktuell
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