Cancer research starts looking toward the microbiome for biomarkers and treatment

Jennifer A. Wargo, MD, MMSc
Jennifer A. Wargo, MD, MMSc

Growing evidence supports findings that changes in both tumor and gut microbiomes play a role in the success or failure of cancer therapies. Preclinical and clinical studies have shown that modifying the microbiome can positively, or negatively, affect response to cancer therapy.

“There is an element of hype, which needs to be tempered, and there is also tremendous hope and opportunity in modulating the microbiome,” said Jennifer A. Wargo, MD, MMSc, The University of Texas MD Anderson Cancer Center.

Wargo moderated the major symposium The Microbiome in Cancer Therapy: Hype or Hope? that is available as an On Demand session now. Presenters will continue their microbiome exploration during a live panel discussion on Wednesday, April 14, from 10 – 10:30 a.m. EDT. When viewing the On Demand session, viewers can submit their questions in a provided Q&A box. All questions submitted before the live session will reach the panelists.

A typical adult human body contains about 30 trillion human and 39 trillion microbial cells, noted Rob Knight, PhD, The Center for Microbiome Innovation at the University of California, San Diego. Each of us has 20,000 human genes and up to 20 million microbial genes. Until recent years, cancer research turned a blind eye to our microbial selves.

Knight, Rob, MD
Rob Knight, PhD

“We are ignoring the 99 percent of our genes that we can change, our microbial genome,” Knight said. “What happens in the gut affects health and disease throughout the body, including cancers.”

Microbes are involved in most hallmarks of cancer and in most types of cancer, Knight said. Bloodborne microbial DNA is strongly predictive for the 33 cancer types included in the TCGA. Clinical trials have shown that modifying the gut microbiome can change immunotherapy response.

Improving cancer therapeutic efficacy is just part of the potential microbiome tool kit. Microbial species can serve as biomarkers for cancer and other diseases. Microbes are already being used as therapeutic agents in fecal microbial transplantation (FMT), and personalized microbial therapeutics are on the horizon.

“We are going into a new revolution in medicine, going from immunotherapy to microbial therapy,” said Siew C. Ng, PhD, Microbiome I-Centre, The Chinese University of Hong Kong. “We are changing our paradigm of cancer pathogenesis, diagnosis, and therapeutics.”

Siew C. Ng, PhD
Siew C. Ng, PhD

At least 20 microbial biomarkers for colorectal cancer (CRC) have already been identified, she said. Adding Fusobacterium nucleatum (Fn) assay to FIT boosts diagnostic accuracy to 95 percent. Fn promotes chemoresistance in CRC by activating autophagy pathways.

Altering the microbiome can change the efficacy of multiple cancer therapies, convert non-responders into responders, reduce treatment-associated toxicity, and influence survival.

A diverse microbiota rich in Akkermansia, Bifodobacterium, Faecalibacterium and certain other species predicts response to cancer immunotherapy. And the use of antibiotics shortly before or during immunotherapy inhibits immunotherapy response in patients with non-small cell lung cancer, renal cell carcinoma, and melanoma.

“We now know that bacterial-mediated interactions with the immune system are essential for optimal drug efficiency, Ng said. “The right microbiome can create a favorable tumor microenvironment to overcome cancer and treatment resistance.”

The mechanistic links between microbiome and clinical outcomes remain murky, Ng said. After more than 600 FMTs and multiple clinical trials, it appears that multiple elements of bacterial, fungal, and viral microbiota play roles in modifying response to disease and treatment response.

“We don’t have the perfect strategies, but we have strong signals,” Wargo said. “It’s not all about the microbiome, but the microbiome is a big part.”