Redrawing therapeutic boundaries: microbiota and cancer

Abstract

The unexpected roles of the microbiota in cancer challenge explanations of carcinogenesis that focus on tumor-intrinsic properties. Most tumors contain bacteria and viruses, and the host's proximal and distal microbiota influence both cancer incidence and therapeutic responsiveness. Continuing the history of cancer-microbe research, these findings raise a key question: to what extent is the microbiota relevant for clinical oncology? We approach this by critically evaluating three issues: how the microbiota provides a predictive biomarker of cancer growth and therapeutic responsiveness, the microbiota's causal role(s) in cancer development, and how therapeutic manipulations of the microbiota improve patient outcomes in cancer. Clarifying the conceptual and empirical aspects of the cancer-associated microbiota can orient future research and guide its implementation in clinical oncology.

Keywords: biomarkers; cancer; causality; microbiota; network medicine; therapeutic modulation.

Figure 1.. Microbiota-tumor-host interactions.

Visual depiction of some key mechanisms and causal pathways being uncovered within the host-tumor-microbiota network.

Figure 2.. Microbiota-Cancer Conceptual Matrix.

This matrix, depicted as a parallel coordinates plot, reflects various conceptual and empirical issues in current microbiota-cancer research while engendering novel questions. For instance, research has shown how the microbiota can play different roles in tumorigenesis and treatment, but it remains an open question whether these roles are based on a particular microbial species, function, or anatomical location, and the precise mechanisms involved are often tentative due to the complexity of the cancer-host interactions. It further remains important to elucidate how these roles and levels intersect with immune-microbiota pathways and whether they are conserved amongst multiple microbes in a particular environment. Next, we can modulate treatments through the targeted use of antibiotics or host nutritional interventions and explore their efficacy in altering not only tumor- or tissue-specific microbiota, but also preventing microbial translocation and the formation of premetastatic niches. Finally, the complexity of causal mechanisms and therapeutic interventions increases as we shift analysis from the TME level to interacting networks or even the entire metaorganism.