The brain tumor form glioblastoma is difficult to treat and it has very poor prognosis. In a new study, published in the record Cell Reports, scientists from Uppsala University show that the type of stem cell in the tumor is present in different declares, with different response to drugs and radiation. The results may open up an avenue towards development of new treatment strategies designed to invert therapy resistant cell states to more sensitive says.

Glioblastoma is a very aggressive growth form and affected patients only survive for, typically, approximately a year after diagnosis. Researchers believe that the difficulties for the disease is caused by cells in the tumors called glioma-initiating cells (GICs), a kind of stem cells that can start developing again, after treatment has been finished.

The brand new results from Uppsala University show that a single tumor included GICs in different states that are differently resistant to therapy. Cellular states that were resistant to radiation were also resistant to medications, and states that were resistant to one drugs tended to be resists most of the other tested drugs.

“Another fascinating result was that the GICs did not fall into distinct reaction groups. Instead the difference in their response can best become a continuum of cells with different resistance levels. We also uncovered a relationship between the resistance level and molecular features of the tumor that are associated with disease prognosis. A proof cell state of the GICs was linked to characteristics connected with poor prognosis and a sensitive cell state was connected to characteristics associated with better outcome, ” says Anna Segerman, who has led the study together with Bengt Westermark, Department associated with Immunology, Genetics and Pathology.

A new technique to treat glioblastoma could be to target the intertumor heterogeneity, we. e. the presence in the same tumor of a mixture of GICs that have different resistance levels and are linked to different prognoses.

“We hypothesize that the mix of GICs with various resistance levels is formed by a drift between the different cellular states. With more knowledge about the mechanisms behind this it could be possible to develop new therapies that reprogram the GICs to render them more sensitive to radiation plus drugs, ” says Bengt Westermark.

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