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Changes in individual cancer cells over time may explain why brain tumors grow so differently and why some cancer cells are resistant to certain treatments. To track the development of cancer cells, researchers at Uppsala University have developed a new method that, in the long term, could facilitate the development of new, effective drug combinations. The research is presented in the journal Molecular Systems Biology.
A brain tumor is made up of many different types of cancer cells with a variety of characteristics, in part resembling cell types found in a healthy brain. Previously, it was difficult to study how this diversity arises. However, its origin has a crucial bearing on the strategy that can be used for drug development. If cancer cells are organized hierarchically, a good approach to shrinking the tumor is to attack cells at the top of the hierarchy. If, on the other hand, cell types are organized more flexibly, other treatment strategies are needed.
To understand how different cell types are organized, we had to develop a method to track individual cells and their offspring over time. We also needed a procedure to quantitatively assess the results, and that is why interdisciplinary collaboration emerged. “
Professor Sven Nelander
The new method was developed in collaboration with Chalmers University of Technology. The scientists combined profiling of individual cells, using a “bar coding” technique, with mathematical modeling and computer simulations. By applying the method to cancer cells from three brain tumor patients, the researchers showed that the organization appears hierarchical, but with a certain flexibility. There are also patient specific characteristics. They also demonstrated that the cellular organization itself is influenced by drug treatment.
“The active substance temozolomide, which is the standard chemotherapy treatment for brain tumors, appears to direct cells against a more invasive cell type. According to our model, temozolomide combined with a drug specifically targeting this cell type should be an effective means of attacking the tumor, ”explains Ida Larsson, PhD, one of the lead authors of the study.
“We believe that this method has great potential. In addition to helping the development of therapies against brain tumors, our method can be used on other types of cancer for which, at present, no method of treatment. effective does not exist. “
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Journal reference:
Larsson, I., et al. (2021) Modeling the heterogeneity of glioblastoma as a dynamic network of cellular states. Biology of molecular systems. doi.org/10.15252/msb.20100105.
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