The Role of the Circadian Clock in Glioblastoma Progression and Treatment

Abstract

Glioblastoma (GBM) is the most aggressive and treatment-resistant malignant brain tumor in adults. Current therapies, including surgery, radiation, and chemotherapy with temozolomide (TMZ), offer subtle improvements in terms of survival. New and upcoming research highlights the role of the circadian rhythm, the body’s internal 24-hour clock, in tumor growth and treatment response. Disruptions in core clock genes such as BMAL1 and CLOCK are common in GBM and have often been linked to increased tumor cell survival and resistance to therapies. Preclinical studies show that targeting the circadian clock, either by inhibiting key clock genes or by timing treatments to align with natural biological rhythms (chronotherapy), can slow tumor progression and improve survival in models. However, clinical trials have shown mixed results, and challenges remain in translating these strategies to practice due to differences in individual circadian timing and various ethical implications about access, safety, and feasibility. Despite these obstacles, the circadian system represents a promising direction for future GBM therapies that may enhance treatment precision and effectiveness.