ecancermedicalscience

ecancermedicalscience es una revista médica de libre acceso (open access), enfocada a las comunidades con menos recursos. Para ayudar a reducir las desigualdades globales en la atención y tratamiento de cáncer, proporcionamos acceso gratuito a todos nuestros artículos y solo cobramos tasas a aquellos autores que cuentan con patrocinios específicos para cubrir costes de la publicación.

La revista considera artículos sobre todos los aspectos de la investigación relacionados con el cáncer, incluyendo biología molecular, genética, fisiopatología, epidemiología, casos clínicos, estudios clínicos controlados (en particular si son estudios independientes o financiados con fondos públicos), sistemas de salud, políticas públicas y los aspectos regulatorios del cáncer. Son de especial interés los artículos centrados en entornos de escasos recursos y la reducción de las desigualdades globales en la atención y el tratamiento del cáncer.

The microbiome – a novel paradigm in oncology research

5 Sep 2018
Guest Editors: James Kinross, Alasdair Scott and Julian Marchesi

James Kinross1,2, Alasdair Scott1,2 and Julian Marchesi1,2,3

1 Department of Surgery and Cancer, St Mary’s Hospital, Imperial College London, London, W2 1NY, UK

2 Centre for Digestive and Gut health, St Mary’s Hospital, Imperial College London, London, W2 1NY, UK

3 School of Biosciences, Cardiff University, Cardiff, CF10 3AX, UK

Correspondence to: Julian R Marchesi

Email: j.marchesi@imperial.ac.uk or marchesijr@cardiff.ac.uk

Global cancer rates are likely to rise by 50% to 15 million by 2020 and the WHO states that 50% of these cases could be prevented. For many years the perception of cancer was that it was a genetic disease, driven by inherited or spontaneous mutations and this theory has informed many of the attempts to stratify cancer therapy and improve cancer outcomes. However, the rapid rise in cancer prevalence and the critical importance of the environment in cancer prevention suggests that this may be an oversimplification, and in fact the majority of sporadic cancers are environmental in their aetiology.

 It is still not clear how the environment triggers cancer initiation in many cancer types, but an unintended benefit of the genomics revolution was to create completely novel technologies for studying the very large and complex ecosystems of bacteria, fungi, viruses and parasites that inhabit the human body. This “jump” was made possible using high-throughput gene sequencing platforms and the birth of ‘metagenomics’ and other “omics” platforms for studying the function of these bacteria. This approach was revolutionary, as “the great plate count anomaly” [1] suggested it was too difficult to grow many of the bacteria that reside within the gut in the laboratory because of their highly specific nutritional and environmental requirements. However, we now know that most bacteria can be grown from faecal samples [2] and that this probably holds true for many other niches in the human body.

The greater understanding underpinned by “omics” technologies has challenged long-held prejudices regarding the role of the human microbiome in the host. For many years these organisms were seen as passengers which opportunistically infected tissues or caused harm through infection or classic pathogenic mechanisms and, apart from a small number of examples, they did not play a role in the causation of chronic disease. However, it is now clear that the relationship between the host and its vast and highly diverse population of organisms is deep, complex, and essential to nearly all aspects of human health. This relationship is based on hundreds of thousands of years of co-evolution resulting in host physiological requirements that can only be serviced by the microbiota. In other words, humans are super-organisms of massive interconnecting genomes from trillions of organisms that are all essential for maintaining health.

Cancer has therefore been studied in significant detail from this “systems” perspective, as it represents a clear example of how microbes may cause chronic disease and it is well established that microbes are the key drivers of certain types of cancer; gastric and cervical cancer for example.  In these two examples the microbes, Helicobacter pylori and human papilloma virus (strains 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) are considered as pathogens and classified as Group 1 carcinogens (http://monographs.iarc.fr/ENG/Classification/).  However, in many cancers, such as colorectal, no clear microbial carcinogen has been identified. With these cancers, we are applying different scientific approaches to try and explain how the microbiota can cause the disease. This requires a different philosophical approach: instead of a pathogenic theory of disease where a single driver organism is responsible, it is the network effect of a community of organisms that is detrimental to the host.

We have therefore started to explore amensalistic relationships that are involved in the causation of cancer. In this scenario one member of the symbiosis grows and causes inadvertent damage to the other member or host, but is not evolved to do this, as a pathogen would. Clear examples of this symbiosis include the production of cyto- and geno-toxic agents such as hydrogen sulphide, protease and phenol, which can be produced by intestinal bacteria and which can cause DNA damage or inflammation, thus increasing the risk of developing cancer. Such functions are much harder to pin down to distinct species and may be emergent properties of a complex community when it is exposed to a specific environmental trigger, such as a dietary component. Thus, these functions are difficult to track and evaluate and are also difficult to abrogate, since within any two individuals they may be the product of very different microbes and circumstances.

With this in mind we have started to catalogue the microbes which are found to be associated with the tumours  in colorectal cancer [3, 4] and to identify the microbial ecology of the disease and to apply a wide range of “omics” platforms to interrogate this relationship. Others are also exploring how the microbiota can influence the response to the novel immunotherapies being developed to treat cancers [5, 6].

In the age of the superorganism it is not possible to have personalised healthcare without considering the microbiome and its significant influence on disease aetiology and treatment efficacy and toxicity. In the next decade the area of the “oncomicrobiome” will therefore develop significantly to establish the role of the microbiota in causation of local and metastatic cancers, but more importantly we will begin to develop novel methodologies for manipulating and engineering the microbiome for precision cancer prevention and therapy.

In this special issue, members of the International Cancer Microbiome Consortium (ICMC, an international collaborative of scientists and clinicians aiming to further microbiome-oncology research) have contributed a series of articles exploring this evolving field [7]. Readers will be taken through the technology and “omics” sciences underpinning microbiome research. We consider more deeply how the microbiome may cause cancer using colorectal and lung cancer as a paradigms. The realisation of the clinical promise of the microbiome is described in an article on pharmacobiomics – the interaction of the microbiome with chemotherapeutics. We also look at the techniques and the potential benefits of microbiome manipulation for therapeutic benefit and concentrate specifically on the potential role of probiotics in cancer therapy. We hope this special issue will provide a solid introduction and broad overview of microbiome-oncology research for clinicians and scientists who may be less familiar with this novel field.  

References

[1]  Staley JT and Konopka A (1985) Measurement of in situ activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats Annu Rev Microbiol 39  321-46

[2]  Browne HP et al. (2016) Culturing of 'unculturable' human microbiota reveals novel taxa and extensive sporulation Nature 533 (7604) 543-6

[3] Kinross J et al. (2017) A prospective analysis of mucosal microbiome-metabonome interactions in colorectal cancer using a combined MAS 1HNMR and metataxonomic strategy Sci Rep  7 (1) 8979

[4] Marchesi JR et al. (2011) Towards the human colorectal cancer microbiome PLoS One 6 (5)  e20447

[5] Gopalakrishnan V et al. (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients Science 359 (6371) 97-103

[6] Routy B et al. (2018) Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors Science 359 (6371) 91-97

[7] Scott AJ et al. (2017) Highlights from the Inaugural International Cancer Microbiome Consortium Meeting (ICMC), 5-6 September 2017, London, UK ecancermedicalscience 11 791

 

Artículos de Edición Especial

Anna Louise Pouncey, Alasdair James Scott, James Leslie Alexander, Julian Marchesi, James Kinross
Saman Maleki Vareki, Ryan M Chanyi, Kamilah Abdur-Rashid, Liam Brennan, Jeremy P Burton
Luis AJ Mur, Sharon A Huws, Simon JS Cameron, Paul D Lewis, Keir E Lewis
James L Alexander, Alasdair J Scott, Anna L Pouncey, Julian Marchesi, James Kinross, Julian Teare
Benjamin H Mullish, Laura S Osborne, Julian R Marchesi, Julie AK McDonald