Watching how cancer cells develop can provide better treatment

How individual cancer cells change over time may explain why brain tumors develop so differently. And also why some cancer cells are resistant to certain treatments. A new method of mapping the development of cancer cells can make it easier to develop new effective drug combinations. A brain tumor consists of a variety of cancer cells, with different properties that are partly similar to cell types found in a healthy brain. How this diversity arises has previously been difficult to study, but is of crucial importance for which strategy can be used for drug development. If the cancer cells are hierarchically organized, it would be tactical to attack the cells at the top of the hierarchy in order to reduce the tumor. However, if the organization between cell types is more flexible, other treatment strategies are needed. New method follows the development of individual tumor cells

– To understand how the different cancer cell types are organized, we had to develop a method to follow individual cells and their offspring over time. We also needed an approach to quantitatively evaluate the results, and therefore an interdisciplinary collaboration emerged, says Sven Nelander, professor of integrative cancer research at Uppsala University.

Cancer cells are organized both hierarchically and flexibly The new method has been developed in collaboration with Chalmers University of Technology. The researchers have combined profiling of individual cells using so-called barcoding – technology with mathematical modeling and computer simulations. By applying the method to cancer cells from three different patients with brain tumors, the researchers have shown that the organization appears to be hierarchical but with a certain degree of flexibility. There are also clear patient-specific elements. They have also shown that the organization itself is affected by drug treatment. New combinations of drugs can attack the tumor – The active substance temozolomide, which is the standard treatment for brain tumors, seems to direct the cells towards a more invasive cell type. According to our model, temozolomide, in combination with a drug that specifically targets this cell type, would be an effective way to attack the tumor, says Ida Larsson, doctoral student and one of the study’s lead authors.

– We believe that this new method has great potential. In addition to helping the development of treatments for brain tumors, our method can be used on other cancers where there are currently no effective treatment methods, she says.

Scientific article:

Modeling glioblastoma heterogeneity as a dynamic network of cell states , Ida Larsson et al (2021), Molecular Systems Biology Contact:

Sven Nelander, Professor of Integrative Cancer Research at Uppsala University, .see

Ida Larsson, PhD student at Uppsala University, ida.larsson@igp.uu.se Erika Dalmo, PhD student at Uppsala University,
erika.dalmo@igp.uu.se

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