Mechanotransduction as a therapeutic target for brain tumours

Despite decades of research, treatment options for many paediatric and adult brain tumours remain inadequate. Mechanotransduction, a process by which cells convert mechanical cues into biochemical signals, resulting in the activation of signalling cascades, is crucial in the progression of aggressive brain tumours such as glioblastoma (GBM). In GBM, a stiffened extracellular matrix accompanies the aberrant expression of mechanosensitive ion channels, including Piezo and transient receptor potential (TRP) channels, impacting brain tumour progression and therapeutic response. Thus, targeting these ion channels and associated signalling pathways may provide effective adjuvant therapy. Focused ultrasound (FUS) is an emerging technology being explored in diagnostic and therapeutic applications within oncology and has the potential to non-invasively modulate mechanosensitive pathways. Here, we discuss recent findings, highlighting how mechanobiology is altered in brain tumours, the potential of mechanosensitive ion channels as therapeutic targets and perspectives on using FUS to exploit aberrant brain tumour mechanobiology to provide non-invasive adjuvant therapy. At the intersection of cancer cell biology and biomedical engineering, this review offers a perspective on leveraging mechanotransduction for therapeutic advances in brain tumours.