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

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.