Tunnelling nanotubes: A bridge for heterogeneity in glioblastoma and a new therapeutic target?

Background: The concept of tumour heterogeneity is not novel but is fast becoming a paradigm by which to explain part of the highly recalcitrant nature of aggressive malignant tumours. Glioblastoma is a prime example of such difficult-to-treat, invasive, and incurable malignancies. With the advent of the post-genomic age and increased access to next-generation sequencing technologies, numerous publications have described the presence and extent of intratumoural and intertumoural heterogeneity present in glioblastoma. Moreover, there have been numerous reports more directly correlating the heterogeneity of glioblastoma to its refractory, reoccurring, and inevitably terminal nature. It is therefore prudent to consider the different forms of heterogeneity seen in glioblastoma and how to harness this understanding to better strategize novel therapeutic approaches. One of the most central questions of tumour heterogeneity is how these numerous different cell types (both tumour and non-tumour) in the tumour mass communicate. Recent findings: This chapter provides a brief review on the variable heterogeneity of glioblastoma, with a focus on cellular heterogeneity and on modalities of communication that can induce further molecular diversity within the complex and ever-evolving tumour microenvironment. We provide particular emphasis on the emerging role of actin-based cellular conduits called tunnelling nanotubes (TNTs) and tumour microtubes (TMs) and outline the perceived current problems in the field that need to be resolved before pharmacological targeting of TNTs can become a reality. Conclusions: We conclude that TNTs and TMs provide a new and exciting avenue for the therapeutic targeting of glioblastoma and that numerous inroads have already made into TNT and TM biology. However, to target TMs and TNTs, several advances must be made before this aim can become a reality.