Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in DIPG: A Review of Current and Future Strategies

Diffuse intrinsic pontine glioma (DIPG) presents a significant challenge in paediatric neuro-oncology due to its aggressive nature and limited treatment options. Typically affecting children aged 5–10 years, DIPG patients have a poor prognosis, with a median survival of less than 1 year. The inoperable nature of DIPG hinders comprehensive molecular analysis, presenting a critical obstacle. Despite scientific advancements, treatment options are limited, and prognosis remains poor, particularly for paediatric patients. This review provides a comprehensive examination of the current landscape of DIPG research, addressing key aspects of diagnosis, molecular understanding, treatment modalities, and emerging therapeutic strategies. The review navigates the complexities of DIPG heterogeneity, emphasizing the need for nuanced approaches in therapeutic interventions. Clinical trials exploring combinations of radiation, chemotherapy, and novel agents, including anti-angiogenic drugs and immunotherapy, are discussed, shedding light on potential avenues of hope. Common genomic alterations in TP53, PDGFRA, and ACVR1 are explored as potential therapeutic targets. Gene therapy, with a focus on immunostimulatory approaches, is under investigation in clinical trials to address the infiltrative nature of DIPG. This review aims to offer a comprehensive overview of the current state of DIPG research, highlighting challenges, advancements, and future directions in the pursuit of effective therapeutic strategies for this devastating paediatric brain tumour.