A landmark study by Wang et al. (Nature, 2024), titled “Integrative Spatial Analysis Reveals a Multi-layered Organization of Glioblastoma,” has transformed our understanding of one of the deadliest cancers. Using state-of-the-art spatial transcriptomics and multi-omics profiling, the authors reveal that glioblastoma is structured into distinct but interdependent zones; a hypoxic, therapy-resistant core; a proliferative middle layer rich in TOP2A-driven replication stress; and an invasive outer rim that interacts with normal brain tissue and evades immune surveillance.

These insights directly support the therapeutic approach pioneered by OncoTherics. Our unidirectional Hypoxia-Activated Prodrugs (uHAPs), such as OCT1002, are designed to selectively release potent TOP2A poisons within hypoxic tumour regions, precisely where Wang et al. identify the most aggressive and treatment-resistant cells. By combining molecular precision with spatial selectivity, OCT1002 has the potential to eradicate the resilient hypoxic core of glioblastoma while sparing normal brain tissue, addressing one of the fundamental challenges highlighted by this study.

In mapping glioblastoma’s hidden architecture, Wang et al. provide powerful validation for OncoTherics’ mission: to exploit the biology of tumour hypoxia and transform it into a therapeutic advantage.