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Mechanotransduction as a therapeutic target for brain tumours.

Authors: Gomes L, Pardo-Pastor C, Rosenblatt J, Pouliopoulos AN

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.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To review recent findings on aberrant mechanobiology in brain tumours and evaluate mechanosensitive ion channels and focused ultrasound as potential non-invasive adjuvant therapies.
Disease model glioblastoma

Outcomes and Safety

Summary of Outcomes Glioblastomas show increased ECM stiffness and upregulation of mechanosensitive ion channels (Piezo1 and certain TRP channels), with chronic activation associated with pro‑tumorigenic signalling. Acute, dynamic focused ultrasound (FUS) can mechanically activate Piezo1 to elicit Ca2+ influx and mitochondrial apoptosis in non‑brain cancer cell lines, suggesting a potential way to kill tumour cells, but FUS effects on Piezo1 in brain tumour cells/in vivo have not yet been demonstrated and no specific FUS parameters were validated in this work.
Safety-related matter The paper does not report specific adverse effects but cautions that FUS can produce mechanical, ablative and thermal effects and that prolonged or inappropriate activation of mechanotransduction (e.g., Piezo1) could inadvertently promote tumour survival/progression; it emphasizes the need for precise control of FUS parameters and further study to ensure treatments do not worsen disease.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

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