Volume 6,Issue 3
Tumour Microtubes and Therapy Resistance in Gliomas Molecular Mechanisms and Therapeutic Opportunities
Gliomas are highly infiltrative primary brain tumours characterised by poor prognosis and frequent recurrence due to therapy resistance. Conventional treatments, including surgery, radiotherapy, and chemotherapy, are often ineffective in achieving long-term control, particularly in glioblastoma, the most aggressive subtype. Recent discoveries have revealed that glioma cells form extensive networks of actin- and myosin-rich membrane structures, termed tumour microtubes (TMs), which enable long-range intercellular communication, calcium wave propagation, and metabolic exchange via connexin 43 (Cx43) gap junctions. These networks facilitate tumour cell survival by supporting self-repair, maintaining calcium homeostasis, and conferring resistance to radiotherapy and temozolomide chemotherapy. GAP-43, a neuronal growth-associated protein, has been identified as a key driver of TM formation, linking glioma biology to neural developmental pathways. Targeting TM networks or Cx43-mediated signalling—through monoclonal antibodies, gap junction inhibitors, or peptide disruptors—has shown promise in preclinical models, particularly when combined with PI3K pathway inhibition to overcome temozolomide resistance. This review synthesises current molecular insights into TM biology, highlights their contribution to glioma therapy resistance, and discusses emerging strategies to translate these findings into effective, tumour-selective therapeutic approaches.
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