Inclusion of microbiome supports Micronoma’s efforts to improve cancer detection
The “hallmarks of cancer” have captured the core features of cancer biology and served as a guide for future research since their original publication in Cell in 2000. Since then, the hallmarks and its 2011 update have been cited collectively more than 95,000 times, indicating the high credibility of these publications.
In 2022, the addition of the “polymorphic microbiomes” in the third installment of this vaunted list —“Hallmarks of Cancer: New Dimensions”—marks an important moment for Micronoma as it seeks to build better cancer diagnostic tests using patients’ microbiomes.
The inclusion stands as a major milestone that should mark an important turn in the road to more discovery in the field, including from researchers who may have previously discounted the role of the microbes in cancer research.
“Many people who have studied cancer using the previous ‘sterile’ hallmarks may have been hesitant to consider a microbial-augmented diagnostic or therapeutic approach,” Micronoma Co-founder and Chief Analytics Officer Greg Sepich-Poore, PhD said. “The new inclusion of microbiomes is a major step forward in addressing some of those people’s concerns and driving future research and clinical breakthroughs.”
Published in Cancer Discovery, one of the top journals of the American Association for Cancer Research, the third version of the hallmarks expanded the 2011 edition with additional “cancer hallmarks” and “enabling characteristics,” including nonmutational epigenetic reprogramming, polymorphic microbiomes, unlocking phenotypic plasticity, and senescent cells. Each of them were included based on new findings collected during the past decade.
The hallmarks represent core features and mechanisms that are shared across many different, though not all, cancer types and have undergirded much of recent cancer research.
The overdue inclusion of the microbes in this list reflects the growing body of literature showing that microorganisms inhabit most major human cancer types, and are involved in immune development and regulation in ways that modulate antitumor immunity. Critically, researchers have found that the success of many kinds of cancer therapies (e.g., immunotherapy, chemotherapy, radiotherapy) is dependent on the presence and activity of the human microbiome.
“All these aspects argue that not considering polymorphic microbiomes in cancer biology would be a failure to actively characterize key contributors to carcinogenesis, drug targets, and therapy resistance,” Sepich-Poore said. Because microbes are related to many of the various cancer development pathways, the presence or absence of microbes also has diagnostic implications.
Micronoma is working to exploit these diagnostic opportunities by looking for microbial cell-free DNA in patients’ plasma to diagnose the presence of cancer. There are several advantages to profiling microbial analytes over human ones, including their inherent diversity (hundreds to thousands of targets), body-site specificity, and the minimal invasiveness of a blood draw. Conversely, other diagnostic tests centered on human analytes have often struggled to show sufficient sensitivity at very early cancer stages, either because there are few markers to use (low diversity) or few of them present (low abundance) in early-stage disease.
The diversity of the microbiome can enhance the sensitivity of microbial-driven cancer diagnostics by its multiplicity of biomarkers. Sepich-Poore likened it to LeBron James being able to take hundreds of shots from the other side of the court in order to make a basket instead of only one attempt.
“If you give LeBron 1,000 shots on goal, you know he’s probably going to make at least one basket. Reducing the number of opportunities reduces the chances of making a basket,” Sepich-Poore said. “It’s kind of similar in our case, since the absolute abundance of nucleic acids being shed into circulation (microbial or tumoral) is very limited. However, the fact that we have many kinds of microbes (hundreds to thousands of features) that one can detect that are associated with cancer presence increases our chances of detection and thereby the sensitivity of the test.”
While research, including the new cancer hallmarks, no longer supports that cancer is simply a ‘sterile’ disease of the genome, not all aspects of the field have adapted to this reality, including the theory of cancer clonal evolution.
“I think the hallmarks paper has, hopefully, opened some people’s eyes that microbes are important entities to consider in the evolution of cancer,” Sepich-Poore said.
In this respect, the latest hallmarks of cancer paper dovetails well with the publication of new article in BioEssays, “Cancer’s second genome: Microbial cancer diagnostics and redefining clonal evolution as a multispecies process,” by Sepich-Poore and fellow co-founder Rob Knight, Ph.D. among others.
“Microbes are not a trivial piece of the cancer biology picture,” Sepich-Poore said. “But it is certainly better to include them, or at least to try to approximately include them, in the current cancer framework than to entirely leave them out and have a theory that is lacking an essential component.”