Glioblastoma Multiforme: A Look Inside Its Heterogeneous Nature

TLDR

Tumor heterogeneity, both inter‑ and intra‑tumoral, complicates diagnosis and therapy, and recent single‑cell advances are enabling deeper study of intra‑tumor heterogeneity. This review focuses on intra‑tumor heterogeneity in glioblastoma multiforme to inform the development of therapies that prevent tumor escape. The authors examine GBM’s cellular and molecular heterogeneity using recent single‑cell technologies and conceptual models such as the tree analogy.

Abstract

Heterogeneity is a hallmark of tumors and has a crucial role in the outcome of the malignancy, because it not only confounds diagnosis, but also challenges the design of effective therapies. There are two types of heterogeneity: inter-tumor and intra-tumor heterogeneity. While inter-tumor heterogeneity has been studied widely, intra-tumor heterogeneity has been neglected even though numerous studies support this aspect of tumor pathobiology. The main reason has been the technical difficulties, but with new advances in single-cell technology, intra-tumor heterogeneity is becoming a key area in the study of cancer. Several models try to explain the origin and maintenance of intra-tumor heterogeneity, however, one prominent model compares cancer with a tree where the ubiquitous mutations compose the trunk and mutations present in subpopulations of cells are represented by the branches. In this review we will focus on the intra-tumor heterogeneity of glioblastoma multiforme (GBM), the most common brain tumor in adults that is characterized by a marked heterogeneity at the cellular and molecular levels. Better understanding of this heterogeneity will be essential to design effective therapies against this devastating disease to avoid tumor escape.