Drug Repurposing for Targeting Cancer Stem-like Cells in Glioblastoma

Area of Science:

• Oncology
• Pharmacology
• Drug Discovery

Background:

• Glioblastoma (GBM) is a highly lethal brain cancer with poor prognosis due to therapy resistance and recurrence.
• Glioblastoma stem-like cells (GSCs) are key drivers of GBM progression, contributing to resistance and recurrence.
• Targeting GSCs is a critical strategy to improve GBM treatment outcomes.

Purpose of the Study:

• To review and discuss the potential of repurposing existing drugs to target GSCs.
• To identify drugs with anti-GSC activity from various therapeutic classes.
• To explore mechanisms of action and translational challenges of repurposed drugs for GBM.

Main Methods:

• Comprehensive literature review of studies evaluating repurposed drugs against GSCs.
• Identification of drugs originally approved for non-cancer indications with demonstrated anti-GSC effects.
• Analysis of drug mechanisms, signaling pathways involved, and combination therapies.

Main Results:

• Several drug classes, including antidiabetics (Metformin), antihypertensives, antimicrobials, and CNS agents, show anti-GSC activity.
• Drugs impairing mitochondrial function (e.g., Metformin, Chlorpromazine) are relevant candidates.
• Repurposed drugs can enhance sensitivity to Temozolomide (TMZ) and target key pathways like Wnt, PI3K/AKT, and STAT3.

Conclusions:

• Drug repurposing is a viable and cost-effective approach to target GSCs in glioblastoma.
• Repurposed agents can reduce GSC viability, decrease stemness, and sensitize cells to TMZ.
• Further research and clinical trials are needed to overcome translational barriers like blood-brain barrier penetration.