Glioblastoma tumors may be less biologically chaotic than previously thought. An international research team mapped more than one million cells and found that cancer cells follow a recurring pattern as tumors develop, across different patients and genetically distinct tumor subclones. The findings could help researchers explore treatments that target several stages of the disease or interrupt the transitions between them.
The study, published in Nature, combined single-cell and spatial analysis, imaging, whole-genome sequencing and tailored computational tools. Researchers examined multiple regions of tumors from 12 patients and used lab-grown mini-tumors to model development. The resulting GBM-Space atlas is freely accessible, according to the report.
The team found that early-stage cancer cells resemble developmental brain stem cells and gather at the tumor’s advancing edge, where the tumor invades surrounding healthy tissue. These cells can give rise to other cancer cell states. As the tumor grows, cells shift toward states associated with injury response and tissue repair, forming an inner layer. In the tumor core, where oxygen is limited, cells move into severely hypoxic states.
The researchers also reported that each stage of this progression is associated with specific immune environments. They suggest that disrupting these environments, targeting early developmental-like cells, or intervening in the gene-regulatory networks behind cell-state changes could offer avenues for future research. The study does not show that these approaches are effective treatments in patients.
A companion Nature study used the same multiomic data to examine gene regulators that drive or restrict transitions between glioblastoma cell states. Its analysis identified regulatory programs and supported a hierarchical pattern of transitions, complementing the atlas’s account of tumor structure and cell progression.
Glioblastoma is an aggressive adult brain cancer whose varied and changing cell states can make treatment difficult. The authors say that this diversity can leave cells behind after treatment, contributing to resistance and recurrence. The new atlas provides a framework for studying how tumor cells change over time and how those changes relate to their location and surroundings.