Robot technology identifies a Parkinsonian therapeutics repurpose to target stem cells of glioblastoma.
Andres Vargas-ToscanoDilaware KhanAnn-Christin NickelMichael HeweraMarcel Alexander KampIgor FischerHans-Jakob SteigerWei ZhangSajjad MuhammadDaniel HänggiUlf Dietrich KahlertPublished in: CNS oncology (2020)
Aim: Glioblastoma is a heterogeneous lethal disease, regulated by a stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells is a clinical need. Methodology: A robotic workstation was programmed to perform a drug concentration to cell-growth analysis on an in vitro model of glioblastoma stem cells (GSCs). Mode-of-action analysis of the selected top substance was performed with manual repetition assays and acquisition of further parameters. Results: We identified 22 therapeutic potential substances. Three suggested a repurpose potential of neurotransmitter signal-modulating agents to target GSCs, out of which the Parkinson's therapeutic trihexyphenidyl was most effective. Manual repetition assays and initial mode of action characterization revealed suppression of cell proliferation, cell cycle and survival. Conclusion: Anti-neurotransmitter signaling directed therapy has potential to target GSCs. We established a drug testing facility that is able to define a mid-scale chemo responsome of in vitro cancer models, possibly also suitable for other cell systems.
Keyphrases
- stem cells
- cell cycle
- cell proliferation
- cell therapy
- cancer stem cells
- single cell
- high throughput
- papillary thyroid
- cancer therapy
- human health
- emergency department
- photodynamic therapy
- small molecule
- signaling pathway
- risk assessment
- gene expression
- genome wide
- adverse drug
- drug induced
- radiation therapy
- robot assisted
- climate change
- locally advanced
- electronic health record
- pi k akt