[HTML][HTML] The microbiome and the hallmarks of cancer

LE Fulbright, M Ellermann, JC Arthur - PLoS pathogens, 2017 - journals.plos.org
LE Fulbright, M Ellermann, JC Arthur
PLoS pathogens, 2017journals.plos.org
The “Hallmarks of Cancer,” proposed by Hanahan and Weinburg in 2001 and updated in
2011, logically define how a normal cell progresses to a tumorigenic state within a complex
neoplastic environment [1]. These hallmark capabilities have given us remarkable insight
into the multistep changes that occur within the tissue microenvironment during cancer
development. However, it has become well established that host-associated microbial
communities, termed microbiota, also play integral roles in modulating various aspects of …
The “Hallmarks of Cancer,” proposed by Hanahan and Weinburg in 2001 and updated in 2011, logically define how a normal cell progresses to a tumorigenic state within a complex neoplastic environment [1]. These hallmark capabilities have given us remarkable insight into the multistep changes that occur within the tissue microenvironment during cancer development. However, it has become well established that host-associated microbial communities, termed microbiota, also play integral roles in modulating various aspects of host physiology. This includes host processes such as cellular metabolism and immune function that become highly dysregulated during carcinogenesis. Perturbations to the microbiota also disrupt these homeostatic processes, promoting the development of numerous diseases including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Helicobacter pylori served as the initial link between bacteria and cancer, when it was discovered that infection predisposed humans to gastric cancer [2]. More recently, fast and inexpensive next-generation sequencing methods combined with research initiatives to support multi-investigator research teams (for example, the National Institutes of Health (NIH)-funded Human Microbiome Project) have revolutionized our understanding of the microbiota and human disease. In parallel, animal models have demonstrated a causal relationship between particular microbes and cancer development through fecal transplants from cancer-bearing mice or inoculation of cancer-associated microbes into formerly germ-free mice. Together, these studies have shown that our resident microbes likely influence the initiation and progression of tumorigenesis by modulating most, if not all, established host factors that comprise the hallmarks of cancer. Further knowledge defining how the microbiota modulates host physiology and disease pathogenesis, particularly in the context of cancer, will provide a framework for the holobiont concept of cancer development and enable the identification of novel microbial targets for preventative and therapeutic strategies. This review will explore how specific members of the microbiota, summarized in Fig 1 and Table 1, influence the hallmarks of cancer.
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