The Microbiome in Drug Discovery: Cancer
Over the course of this series so far we’ve looked at the role of the microbiome in two of the three major therapeutic areas targeted by drug discoverers. Now comes the third and final segment and it’s a big one: Cancer. For many people the role of the microbiome in inflammation and metabolism is unsurprising. Your immune system reacts to bugs, hence inflammation, and a huge meta-organ living in your gut is going to affect your energy usage so metabolism has to change too, but the importance of the microbiome in cancer often comes as a shock. A big mass of proliferating cells spreading and eventually invading throughout the body, how are bacteria able to control that? However, as is often the case in science, what appears counter-intuitive is actually perfectly logical when you look at the facts. Dr. Andrew Johnson from the University of California is going to talk us through them.
Here’s a fact that might surprise you about cancer. Roughly 18% of cancers worldwide are caused by known pathogens, such as a bacteria or a viruses, which infect us.1 Helicobacter pylori and Human Papiloma Virus are good examples of this. So the idea that microbes could be targeted for cancer treatment is not so new. However, what has emerged more recently and caught people by surprise is the idea that resident bacteria, like the ones in your gut all the time, can also effect cancer growth and development. Similar to inflammatory and metabolic disease, the first hints to this came from experiments with germ free or antibiotic treated mice, which are both resistant to many cancers1-2. Now the application of next generation DNA sequencing to compare the microbiomes of cancer patients, their tumours and healthy controls promises to associate further specific bacteria with human disease.3 Once upon a time these experiments were very hard to do, now the growth of outsourcing opportunities through companies like these listed by Scientist have made it easy and traditional microbiological techniques allow for detailed follow up. The attention of drug discoverers though has already turned to how the microbiome affects cancer. Well, cancer is rarely caused by just one thing. It usually takes multiple “hits”, such as DNA mutations, before a cell proliferates beyond control. What bacteria do, be they pathogens or resident, is increase your risk of collecting these hits. They do this in many ways. By damaging epithelial barriers which naturally proliferate a lot and so are at risk of becoming cancerous anyway, by activating inflammatory pathways that drive cells to proliferate more, and by producing reactive molecules, such as oxygen species or genotoxins, which directly cause DNA damage.1 Furthermore, losing particular functions of the microbiome such as the ability to breakdown carcinogens or produce anti-oxidants such as polyphenols, may also increase cancer risk. All that now remains to be seen is whether we can manipulate this knowledge of the microbiome to develop new, effective, anti cancer drugs.
- Schwabe, R and Jobin, C. (2013), “The Microbiome and Cancer”, Nature Reviews Cancer, vol. 13, pp800-812
- Sears, C and Garrett, W. (2014), “Microbes, Microbiota, and Colon Cancer”, Cell Host & Microbe, vol. 15 pp317-328
- Grivenniko, S. I., (2012), “Inflammation and colorectal cancer: colitis-associated neoplasia”, Seminars in Immunopathology