Mechanisms of cell competition in glioblastoma: A narrative review

Abstract

Cell competition among neighboring cells in a tissue gauges relative fitness in terms of growth and proliferation, which results in the death of cells with suboptimal fitness and the dominance of optimally or supraoptimally fit cells. It is conserved across multiple taxa and has indispensable functions in development, homeostasis, aging, and prevention of neoplastic growth, both in Drosophila and mammals. However, similar to how several key developmental pathways are subverted in cancer, cell competition mechanisms are often co-opted in the oncogenic transformation of cells in homeostatically stable tissues, and the role of this phenomenon in human cancer is attracting increasing interest. Grade IV glioblastomas (GBMs) are the most aggressive brain tumors that occur in adults. GBMs arise from glial cells and invariably result in tumor recurrence and death. Treatment of GBMs is complicated by the unique features of the anatomical context, including the dura, blood–brain barrier, glioma stem cells, necrosis, and extensive genetic and epigenetic heterogeneity. In this review, we discuss the evidence for cell competition elicited by genomic alterations in several key genes involved in early or late gliomagenesis, as well as activation of specific signaling pathways that aid competitive interactions with nonglial cell types like neurons to gain leverage in the colonization of brain niches. The role of intratumoral heterogeneity in conferring clonal dominance or cooperation resulting in therapeutic resistance in GBMs is also discussed.