Cancer stem cell plasticity in glioblastoma multiforme: a perspective on future directions in oncolytic virotherapy

Area of Science:

• Oncology
• Virology
• Cancer Stem Cell Biology

Background:

• The cancer stem cell (CSC) hypothesis posits that a small CSC population drives tumor growth.
• Oncolytic viruses (OVs) offer targeted therapy for solid tumors like glioblastoma (GBM), especially treatment-resistant types.
• Clinical translation of OV efficacy has been limited, potentially due to oversimplified assumptions about CSCs.

Purpose of the Study:

• To review evidence on CSC plasticity and its implications for OV therapy.
• To propose a novel perspective on the clinical trial failures of advanced OV treatments.
• To highlight the importance of preventing CSC regeneration for long-term OV efficacy.

Main Methods:

• Literature review of studies investigating CSC plasticity.
• Analysis of CSC hypothesis in the context of OV treatment failures.
• Formulation of a new perspective on OV clinical trial outcomes.

Main Results:

• Emerging evidence challenges the CSC hypothesis by demonstrating CSC pool regeneration from non-CSCs post-treatment.
• This CSC plasticity may explain the limited success of OVs in clinical settings.
• The ability of non-CSCs to dedifferentiate into CSCs undermines the strategy of solely targeting existing CSCs.

Conclusions:

• Preventing the dedifferentiation of non-CSCs into CSCs is crucial for successful OV therapy.
• Future OV clinical trials must consider and address CSC plasticity to improve treatment outcomes.
• Targeting CSC regeneration pathways may be key to achieving durable responses in GBM and other solid tumors.