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The Assessment of Glioblastoma Tumorspheres Reveals Molecular Determinants of Proliferation and Therapeutic Response

  • Author(s): Laks, Dan RIchard
  • Advisor(s): Kornblum, Harley I
  • Plath, Kathrin
  • et al.
Abstract

Glioblastoma (GBM) is one of the most lethal cancers and new therapies are urgently needed. One key limitation in the development of therapeutics is the availability of appropriate in vitro models in which key molecular pathways can be identified and potential novel therapies can be tested. One model of GBM is through the growth of “tumorspheres”, patient derived GBM cultures grown in neurosphere conditions that generally grow as non-adherent spheres of cells. We assessed gene expression profiling, in vitro phenotypes, and patient survival from a large cohort of high-grade glioma tumorsphere cultures. Through interrogation of the tumorsphere model system, we discovered molecular determinants of proliferation (PTGR1, EFEMP2, LGALS8), effective combinatorial treatment targeting ERK and mTOR, and a mechanism of resistance to chronic mTOR inhibition through GSK3B and MAP1B.

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