Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

Area of Science:

• Oncology
• Pharmacology

Background:

• Paediatric acute myeloid leukaemia (AML) is a complex cancer with limited treatment advancements due to a lack of targeted therapies.
• Standard paediatric AML treatments have seen minimal change for over 40 years, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To identify novel combination therapies for paediatric AML by screening FDA-approved drugs.
• To leverage multiplex screening to discover cost-effective and efficient drug repurposing strategies for paediatric AML.

Main Methods:

• Developed and utilized the Multiplex Screening for Interacting Compounds in AML (MuSICAL) strategy.
• Screened all pairings of 384 FDA-approved compounds using an in-house algorithm, pooling 10 drugs per well.
• Employed a cost-effective approach to maximize the identification of synergistic drug combinations.

Main Results:

• Identified a promising triple combination therapy for paediatric AML.
• The identified combination includes glimepiride, pancuronium dibromide, and vinblastine sulfate.
• Demonstrated the potential of drug repurposing for rapid clinical translation.

Conclusions:

• The MuSICAL screening strategy efficiently identifies potential combination therapies for paediatric AML.
• Drug repurposing offers a viable pathway for developing new treatments for paediatric AML.
• The identified triple drug combination warrants further investigation for clinical application in paediatric AML.