Emerging therapies for glioblastoma

Area of Science:

• Neuro-oncology
• Cancer Therapeutics
• Precision Medicine

Background:

• Glioblastoma (GBM) has a poor prognosis with limited survival despite standard treatments.
• Key challenges include drug resistance, tumor heterogeneity, and the blood-brain barrier.
• Current research focuses on overcoming these obstacles for better therapeutic outcomes.

Purpose of the Study:

• To review recent advances in glioblastoma treatment strategies.
• To highlight emerging therapeutic targets and precision approaches.
• To discuss the role of multi-omic profiling and adaptive clinical trials.

Main Methods:

• Review of targeted therapies (e.g., EGFR, FGFR inhibitors).
• Investigation of pathway modulators (e.g., JAK/STAT, PARP, PI3K/AKT/mTOR).
• Exploration of immunotherapy combinations (e.g., checkpoint inhibitors, oncolytic viruses, CAR T-cells).
• Integration of precision oncology platforms (organoids, functional drug testing).
• Utilization of adaptive clinical trial designs (e.g., GBM AGILE).

Main Results:

• Targeted agents show promise in specific molecular subsets (BRAF V600E, NTRK fusions).
• Immunotherapy efficacy is limited as monotherapy but under investigation in combinations.
• Precision oncology platforms are refining treatment selection and combination strategies.
• Adaptive trials accelerate novel agent evaluation in stratified cohorts.

Conclusions:

• Future glioblastoma treatment likely involves biomarker-informed, multimodal regimens.
• Integration of targeted agents, novel immunotherapies, and precision strategies is crucial.
• Embedding translational endpoints in trial design is essential to address resistance and complex biology.