Gregory Poore is an MD/PhD candidate funded by the NIH’s Medical Scientist Training Program grant who is working in Rob Knight’s lab to bring together two fields that do not frequently communicate: oncology and microbiology. His passion for the subject originates from losing his grandmother, who over the course of 4 weeks in 2013, went from a sudden diagnosis of pancreatic cancer to passing despite targeted chemotherapy. This catalyzed his research in cancer genomics at Duke-NUS (Singapore), where his work was co-authored in multiple publications across Nature Genetics, Genome Medicine, and Leukemia. Upon his return to Duke University in the USA, his research interests broadened to include infectious disease genomics, machine learning techniques, and multi-omic integration. When the first major cancer microbiome paper was published in September 2017, showing chemo-degrading bacteria living in more than half of pancreatic cancer patients, the message hit close to home and his subsequent research focus was decided. His strategies of study to characterize, predict, and treat the cancer microbiome extend from bioinformatics and machine learning to histopathology and technology development.
Please tell us how and to what capacity are you involved with R&D in the cancer-microbiome intersection.
In the field’s current infancy, my focus has primarily been the widespread characterization of the cancer-microbiome across many cancer types and stages. This has involved a combination of retrospective analyses on large cancer genomics datasets or archived patient samples and prospective studies on resected tumors as well. Retrospective analyses have been particularly powerful given the sample sizes already collected for many past cancer genomics datasets, although they require care when addressing non-biological technical variation. My eventual goal is to translate and commercialize this knowledge into microbial based diagnostics, prognostics, and bioengineered therapeutics for cancer.
Why should the healthcare and pharmaceutical communities be excited about learnings from the role of the microbiome in cancer?
Decades of research have studied cancer as a host-based disease, often to find nuanced differences between cancer tissues and their normal counterparts, especially in its early stages. Despite advancements in molecular characterization, cancer (and its many forms) still remains difficult to treat without incurring adverse side effects; even immunotherapy has struggled with this, at times creating life-long autoimmune disorders. The tremendous value of microbiome in cancer is that it provides an orthogonal way to diagnose and treat the disease. Recent research has even shown the opportunity to cure some of these adverse effects caused by immunotherapy, in addition to influencing its efficacy.
In your opinion, what is the biggest bottleneck holding cancer-microbiome research progress back from success?
From my standpoint, success for a life sciences field requires effective clinical translation of its research progress into improving patient outcomes. Practically-speaking, this means diagnosing cancers earlier, reducing their drug resistance, and improving survival on the basis of cancer-microbiome information. Much of this is already happening in select laboratories but the clinical story remains behind, in part because carcinogenesis is largely taught and viewed as a host-based, aseptic process, even in medical schools today. The unrecognized reality is that our bodies are primarily microbial -- roughly 40% human by cell count or 1% human by gene count -- and cancers are intimately involved with its microbial constituents.
What one development or breakthrough would you like to see that would increase our understanding of the impact of the microbiome in cancer and accelerate the translation of research into the clinical setting?
The mainstream introduction of immunotherapy has made a tremendous impact for cancer patients, at times curing them of their disease. The established link between the host’s gut microbiota and immunotherapy efficacy has therefore been an important one since just 20-40% of patients respond. Yet, these findings still treat the tumor microenvironment as a sterile entity and have not fully explained why neoantigen peptides with substantial homology to microbial antigens are found in such tumors. The breakthrough that I would like to see is thus how the intra-tumoral microbiome is influencing immunotherapy response.
Going into the 1st Microbiome Movement – Oncology Response Summit, what do you hope to achieve as part of this dedicated community?
My original foray into medicine and translational research began by rapidly losing my grandmother to chemo-resistant pancreatic cancer, and this experience has shaped much of my past and current work. As pancreatic, colon, lung, liver, and other cancer types continue to be recognized for having significant microbial constituents, it is my hope that this community can help accelerate innovative diagnostics and therapeutics from the bench to commercialization and clinical implementation. It will be challenging, but there is real promise to benefit patients and to do so in the next 5-10 years.
A huge thank you to Gregory Poore for taking the time to share his insights with The Microbiome Movement. Download the Microbiome Movement - Oncology Response brochure to see more details of Greg's talk in Boston July 2019.
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