The emergence of novel targeted anti-cancer agents over the past two decades has transformed the therapeutic landscape of cancer, with these drugs achieving higher efficacy compared to traditional chemotherapies. However, their clinical benefit is often limited by dose-limiting toxicities that negatively impact people’s quality of life and adherence to treatment, ultimately compromising survival outcomes. Increasingly, the gut microbiota is recognised as a key regulator of host responses to cancer therapies, dictating both the efficacy and toxicity of these treatments, reflecting its profound control over multiple “gut-organ” axes. Among these, gut-neural interactions are particularly compelling, with the gut microbiota well known to communicate bidirectionally with enteric, autonomic and central nervous systems.
Accordingly, the gut microbiota has been causally implicated in peripheral neuropathy caused by common conventional chemotherapies, paclitaxel and oxaliplatin. This presentation will provide an updated perspective on the emerging evidence base implicating the gut-neural axis in the neurotoxic side effects of targeted agents, with a focus on the proteosome inhibitor, bortezomib. It will provide an overview of the mechanisms by which the gut microbiota interact with autonomic and peripheral nervous systems, how disruption of this finely balanced axis can lead to neuropathy before showcasing new data that highlights the profound ability of microbial manipulation to eradicate behavioural deficits of neuropathy, without necessarily needing to prevent nerve damage. Threse data form a compelling case for how microbiota-based therapies could be incorporated into neuroprotective supportive care strategies, making targeted therapies more tolerable, improving the depth of tumour control, and ultimately improving survival outcomes and quality of life of people affected by cancer.