Human cerebrospinal fluid affects chemoradiotherapy sensitivities in tumor cells from patients with glioblastoma

Authors: Brett W. Stringer, Manam Inushi De Silva, Zarina Greenberg, Alejandra Noreña Puerta, Robert Adams, Bridget Milky, Michael Zabolocki, Mark van den Hurk, Lisa M. Ebert, Christine Fairly Bishop, Simon J. Conn, Ganessan Kichenadasse , Michael Z. Michael, Rebecca J. Ormsby, Santosh Poonoose, and Cedric Bardy

Science Advances, 25 Oct 2023

Scientists explore the impact of CSF on glioblastoma and use Maestro MEA to evaluate preclinical toxicity of potential therapeutics in vitro.

Some evidence suggests that exposure to cerebrospinal fluid (CSF) may play a role in glioblastoma (GBM) progression, plasticity, and treatment resistance, but the underlying molecular mechanisms are unclear. In this study, researchers use a multiplatform approach to assess the impact of CSF on glioblastoma (GBM) tumors from 25 patients, investigate why GBM is often more resistant to therapies than non-CNS tumors, and identify a potential therapeutic approach.

Overall, the results showed that CSF exposure in the human brain microenvironment promotes tumor cell plasticity and induces resistance to standard treatments. The scientists also found “that inhibiting the transcriptional regulator NUPR1 can improve the efficacy of current chemoradiotherapies for GBM in a neuronal microenvironment,” and used Axion’s Maestro MEA platform to evaluate preclinical toxicity of potential GBM therapeutics in vitro. According to the authors, combining the repurposed antipsychotic trifluoperazine, which inhibits NUPR1, with standard GBM treatment may improve patient survival.