The Molecular Landscape of Glioblastoma: Implications for Diagnosis and Therapy

Glioblastoma, classified as grade IV astrocytoma by the World Health Organisation, is the most common and malignant primary brain tumour in adults, with a high mortality rate. It accounts for 14.5% of central nervous system tumours and 45.6% of primary malignant brain tumours, with an annual incidence of 3.19 per 100,000 people. Despite advances in our understanding of its molecular biology, patient outcomes remain poor, with a median survival of approximately 1 year. Glioblastoma is categorised into four subtypes: IDH wild-type, IDH mutant, not otherwise specified (NOS), and not elsewhere classified (NEC), each affecting prognosis and treatment. Key molecular alterations include IDH1/2, ATRX, TERT, TP53, B-RAF, EGFR, MGMT, and PTEN mutations, which contribute to tumour behaviour and therapeutic targets. Current diagnostic methods, including magnetic resonance imaging and advanced molecular imaging, aid in accurate diagnosis and treatment planning. Although existing therapies offer limited survival benefits, novel treatments like immunotherapy, oncolytic viral therapy, and targeted molecular therapies, are currently being investigated. These emerging therapies overcome challenges such as the blood-brain barrier and tumour heterogeneity, providing hope for improved outcomes. Future perspectives emphasise the importance of integrating molecular biomarkers, optimising treatment strategies, and enhancing clinical trial designs to develop more effective therapies for patients with glioblastoma.This review aims to delve into the intricate facets of glioblastoma, including its classification, histopathology, interactions with the microenvironment, molecular pathogenesis, diagnostic imaging techniques, clinical progression, current therapeutic approaches, challenges in treatment, identifiable risk factors, and exploration of emerging therapies and prospects in glioblastoma management.