Multi‑institutional teams reported that longitudinal tumor biopsies in recurrent glioblastoma provide pharmacodynamic and immune‑response signals not captured by routine MRI. A Mass General Brigham study in Science Translational Medicine demonstrated that serial multiomics sampling safely revealed intratumoral changes during therapy; a Break Through Cancer team showed the oncolytic virus CAN‑3110 elicits deep immune activation within tumors. Investigators argue serial sampling can distinguish true progression from treatment‑related inflammation (pseudoprogression) and can validate target engagement for immunotherapies and oncolytic agents. The studies emphasize that standard imaging may underrepresent biologic responses and that incorporating molecular tissue readouts could refine trial endpoints and patient selection. These findings support integrating scheduled tumor sampling into clinical trials for brain tumors to accelerate therapeutic optimization and regulatory decision making.