Glioblastoma Multiforme (GBM) is one of the most lethal malignant primary brain tumors owing to their heterogeneity and self-renewal capacity. The Glioma stem cell (GSC) population is resistant to all the available conventional therapies which demands an urgent need to develop alternative therapeutic strategies. Specific targeting of Cancer Stem Cells (CSCs) with chemotherapeutics still remains a major challenge in the different categories of brain tumor. Cisplatin, the most widely used chemotherapeutic, is rarely used against brain tumors due to the development of resistance, and toxicity associated with this drug.  We recently discovered in patient derived GSCs of varied background that they utilize fatty acid oxidation (FAO) as a major pathway for their growth and survival. Preliminary studies show that inhibition of this metabolic pathway leads to downregulation of the stemness characteristics of the GSCs. Thus, we embark on a journey to find a nano-therapeutic strategy which can inhibit FAO in GSCs and make this population vulnerable and less stem-cell like. Through a serendipitous discovery, we found that a cisplatin prodrug, has the ability to alter FAO in a series of cancer cells including GSCs. We also recently reported brain penetrating properties of a biocompatible polymeric nanoparticle which has the ability to load these cisplatin prodrugs. In this presentation, we will present the primary findings using this platform to set a stage for potential translation of a targeted nanoparticle delivered cisplatin prodrug to attack GSCs as an alternative treatment approach for GBM.

Inhibition of fatty acid oxidation results in reduced stemness of glioma stem cells

2019 Spring National Meeting

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