Shaping death: how the microbiome regulates tumour cell demise and therapy response

Cell death is a fundamental process that maintains tissue homeostasis and shapes the tumour microenvironment. Cancer cells often evade or reprogram cell death pathways, which leads to malignancy and therapy resistance. On the other hand, the cell death of non-malignant cells significantly influences the adverse effects of anticancer therapy, such as the onset of mucositis or enteritis. Emerging evidence identifies both the tumour and gut microbiomes as critical modulators of these processes. In turn, cell death reshapes the microbial ecosystem by altering nutrient landscapes and immune signalling. Although both cell death and the microbiome are well-studied in cancer, their intersection remains underexplored. This review article addresses this gap by summarising how microbes and microbial metabolites modulate cancer cell death pathways and shape responses to anticancer therapy. We integrated current knowledge on this complex interplay, focusing on key metabolic mediators that can influence cell fate decisions. Understanding this bidirectional crosstalk offers new opportunities to "preserve the good and eliminate the bad" within the tumour-microbiome axis, paving the way for precision microbiome-informed cancer therapies.