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Current Oncology
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29 December 2025

Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma

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1
Department of Synthetic Neurotechnologies, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow 117513, Russia
2
Federal Center of Brain Research and Neurotechnologies, Federal Medical Biological Agency, Moscow 117513, Russia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Curr. Oncol.2026, 33(1), 19;https://doi.org/10.3390/curroncol33010019 
(registering DOI)
This article belongs to the Section Neuro-Oncology

Simple Summary

This review provides an overview of current and emerging glioblastoma treatment approaches, with particular attention to combination therapies and the reference models used to assess their effectiveness. Identifying true synergistic effects between therapeutic agents is critical for improving patient outcomes. Properly designed reference models that reflect the mechanisms of action across preclinical and clinical stages can significantly enhance the interpretation of experimental data. A deeper mechanistic understanding and more accurate modeling will ultimately accelerate the translation of promising combination therapies into effective clinical strategies for managing malignant gliomas.

Abstract

Glioblastoma is currently an incurable disease despite the development of a wide variety of therapeutic approaches, from surgical methods to immunotherapy. In current clinical practice, treatment typically involves a combination of existing methods, often comprising three stages: tumor resection, radiotherapy, and chemotherapy. Modern research offers improved chemotherapy strategies, as well as combinations of chemotherapy with immunotherapy. However, the efficacy of these therapies is profoundly influenced by factors such as tumor and peritumoral heterogeneity, alongside complex molecular signaling pathways. Optimizing glioma treatment requires a rigorous mechanistic understanding of individual approaches and their synergistic effects. This review comprehensively details current glioblastoma therapeutic strategies and critically evaluates key reference models for assessing combination therapy efficacy and their inherent limitations. A deeper understanding of these mechanisms and models will refine the investigation of observed therapeutic effects and accelerate the translation of promising in vitro approaches to effective clinical management of malignant gliomas.

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