Impact of microbiome on head and neck cancers

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Published: 25 Apr 2018
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Dr Young Jun Kim - Vanderbilt-Ingram Cancer Center, Nashville, USA

Dr Kim speaks with ecancer at AACR 2018 about the impact of dysbioses in head and neck squamous cell carcinoma.

He discusses the significance of sample sequencing and how elements of the microbiome may be a marker of cause of disease onset.

Dr Kim goes on to consider the potential of Fusobacterium as a target of disease control.

This is work that came out of a very excellent collaboration during my employment at Johns Hopkins Hospital. I worked there for about eleven years and I had a group of fantastic collaborators, scientists. The person who drove this project is essentially Dr Rafael Guerrero and he is a fellow who worked at Johns Hopkins who really wanted to understand what is the cause and what are the drivers of cancer in head and neck in human side as well. I know he had some mouse model systems but we really wanted to study human head and neck cancer. One of the best tools that he had at his disposal was sequencing – fantastic technologies, wonderful technologies on next generation sequencing or NGS, as it’s appropriately termed. He used this methodology to really provide a more complicated picture than a cancer cell becoming genetically altered and then becoming cancer cells.

Have you found a link between the microbiome and cancer?

It’s fascinating and our work is concordant with a lot of other people’s work, whether it be breast cancer, colon cancer. That is that the microbiome around the tumour, and always also the microbiome outside of the cancer area, plays an important role in whether the cancer progresses or may be more better contained by their immune system. So it’s not just the tumour cells that undergo genetic changes and it becomes more aggressive with genetic changes, it’s much more complicated than that. The cancer cells play a communal role with immune cells as well as the microbiome. We don’t really know exactly yet in head and neck cancer whether this is pro-carcinogenic or anti-carcinogenic but the implication is that we have to account for the microbiome in head and neck cancer.

What are the main challenges to overcome?

The challenge is we know that it’s important for head and neck cancer but we don’t know the mechanism. For this we probably have to go back into the bench-side. We need more scientists like Dr Guerrero to actually query the important questions and go into mice or in vitro culture dish or other tumour models to really tease out what is the role of the microbiome. Is it an offshoot of the presence of the cancer, and if that’s the case it becomes an excellent biomarker potentially that we can study, or do they play an important pathogenic role in the development and the progression of the cancer.

So what’s the next step for this research?

The future, I would imagine, is going back to the mice system. The work basically showed that we have a few candidate flora that is highly enriched for advanced head and neck cancer, namely Fusobacterium is fifty-fold higher in the advanced tumours versus the early stage or normal tissue. So we know that the samples derived from our head and neck cancer patients, they’re telling us something. What we need to do is go back and test whether Fusobacterium can have a promoting role in the mice system and prove this is the case.

What if you found it was the case?

If it is, if Fusobacterium has a potential driver of oncogenesis then these bacteria can be controlled; we have an easy way of controlling them with antibiotics. So that has tremendous implication. The other potential problem is that some of these bugs may grow out from excessive antibiotics use. So I can’t see how we’re going to change our antibiotics use but we need to go back into the experimental system and do more of the wet bench-work.

Who was involved with you for this work?

I just wanted to really score Dr Rafael Guerrero who really led the work. He was a leader in bringing all the team together. We had a team of geneticists, surgeons as well as molecular biologists to really drive this project forward.