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Thu, Dec 7 1:27pm · Microbiome emerges at the frontier of precision medicine

Our genes help determine what makes us unique, such as our eye color, height and whether we are left- or right-handed. But did you know that you also have a unique community of bacteria that live in and on your body, known as your microbiome?

Research has shown that a person’s microbiome affects their health and susceptibility to disease. Your microbiome can be influenced by medications or diet. That’s why microbiome research holds promise for developing individualized approaches to treating a wide range of diseases.

In the latest issue of Mayo Clinic Proceedings, Mayo Clinic researchers reviewed the importance of the microbiome as a key component of personalized medicine to improve diagnosis, reduce disease risk and optimize early detection and treatment. The microbiome is the combined genetic material of the microorganisms in a particular environment.

Purna Kashyap, M.B.B.S.

“The ability to characterize the microbiome, which includes microbes that reside within and upon us and all their genetic elements, using next-generation sequencing allows us to now incorporate this important contributor to human disease in developing new preventive and therapeutic strategies,” says Purna Kashyap, M.B.B.S., a Mayo Clinic gastroenterologist, associate director, Mayo Clinic Center for Individualized Medicine Microbiome Program and lead author of the review.

Potential role of the microbiome in human disease

Here are some applications which highlight the role of the microbiome at the frontier of personalized medicine:

  • Microbial fingerprints could serve as precise, noninvasive, accessible and economical tools that could be used for personalized disease diagnosis, including phenotypes (observable physical characteristics of an individual) severity and prognosis.
  • The role of the microbiome in the metabolism of many chemical compounds makes it a key player in determining drug availability, effectiveness and harmfulness. This could be indispensable for developing personalized drug therapies.
  • The ability to change the microbiome makes it appealing in developing personalized treatment approaches targeting specific microbial pathways tailored to an individual’s microbiota. This may help development of treatments for disorders such as inflammatory bowel disease, obesity and diabetes.
  • Other possibilities include altering the microbiome by using genetic engineering approaches, next-generation prebiotics selectively fermented by gut microbes that confer a health benefit, personalized dietary therapies such as microbiome markers to optimize dietary interventions, and changing the diet based on the microbiome.

Watch: Mayo Clinic offers insights on the microbiome at the frontier of personalized medicine.

Dr. Kashyap expands on the promise and challenges of microbiome research here. 

Mayo Clinic Proceedings Symposium on Precision Medicine 

This paper is the eighth in the Mayo Clinic Proceedings Symposium on Precision Medicine, a series of articles that cover a wide range of topics in personalized medicine. Watch for upcoming articles in the symposium, which will focus on how personalized medicine and genomics are impacting patient care. Learn more about the series.

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See highlights from our recent Individualizing Medicine Conference 2017: Advancing Care Through Genomics:

Save the date for next year’s Individualizing Medicine Conference. It will be held September 11-12, 2018 in Rochester, Minnesota.

 

Mon, Sep 25 11:08pm · Study evaluates effectiveness of deep genomic profiling in clinical setting

Genomic profiling is used today for patients with advanced cancers to help develop new ways to diagnose and treat their disease and offer an individualized treatment plan. While gene panel testing is relatively commonplace, there are many barriers to using new and more sophisticated DNA technologies.

According to Mitesh Borad, M.D., an oncologist at the Mayo Clinic campus in Arizona, there are two key obstacles to applying advanced DNA testing to cancers.

First, this type of approach is cost prohibitive for many patients. Insurance coverage is inconsistent for whole exomes, RNA sequencing and structural genomic assays and some patients may have to pay out-of-pocket.

Second,  it takes a large multi-disciplinary team (bioinfomaticians, lab scientists, oncologists) typically found only at large academic cancer centers.

Mitesh Borad, M.D.

To better understand these obstacles, Dr. Borad and a team of researchers pursued a genomic deep dive using clinical grade testing to better understand the impact.

The study, in Nature Scientific Reports, represents one of the earliest published efforts to date of Clinical Laboratory Improvement Amendments (CLIA)-enabled integrated deep genomic profiling for the identification of therapeutic targets in patients with advanced cancer.

The researchers pursued three objectives:

  1. Determine how much time it takes to complete integrated whole exome/long insert whole genome/transcriptome sequencing.
  2. Estimate how much time it takes to report results of therapeutically relevant drug targets derived from integrated whole exome/long-insert whole genome/whole transcriptome sequencing, along with CLIA validation.
  3. Determine process of drug access.

As a result of the study, researchers determined integrated genomic profiling in a CLIA enabled workflow was successfully demonstrated in a consistent fashion in patients with complex disease diagnosis.

“It is anticipated that with development of faster sequencing, better informatics tools and automation and drop in costs (e.g. recent announcement of potential for a $100 genome) that this will become more broadly applicable and the work presented in the study along with other complementary efforts in the field will lay a groundwork for future activities,” says Dr. Borad.

The study also provides a contextual framework to incorporate other genomic analyses into the workflow as therapeutics using these approaches enter the clinic and their role in therapeutic response prediction is better defined.

This study was supported by: NIH/NCI 1DP2CA195764, and the Mayo Clinic Center for Individualized Medicine. Dr. Borad has been involved in implementation of genome wide assays into molecular profiling efforts in early phase studies since 2007.

Register to attend Individualizing Medicine 2017 and learn more about pharmacogenomics 

Join us to learn more about bringing precision medicine into practice at Individualizing Medicine 2017: Advancing Care Through Genomics.

The Mayo Clinic Center for Individualized Medicine is hosting the sixth annual genomics conference October 9–10, in Rochester, Minnesota.

Explore all conference offerings:

Mayo Clinic Center for Individualized Medicine is hosting the conference with support from the Jackson Family Foundation.

Tue, Sep 19 6:00am · How does a genomic tumor board impact patient care?

The outcomes from a Mayo Clinic study published in Oncotarget found value in having an established genomic tumor board, and using genomics for certain patients.

The experience of the Genomic Tumor Board has promoted an evolution in the practice according to Alan Bryce, M.D., a Mayo Clinic oncologist, and co-first author on the study.

“There is an emerging consensus to begin genomic analysis early in the treatment course due to many driver mutations presenting early in the disease course. This allows time for potential therapies in a clinically useful timeframe,” says Dr. Bryce.

Alan Bryce, M.D.

Mayo researchers looked at initial results from their efforts in establishing the Mayo Clinic Genomic Tumor Board. The board brings together physicians, research scientists, cancer biologists, ethicists, pathologists, bioinformaticians and genetic counselors from Mayo Clinic campuses in Arizona, Florida, and Minnesota. This “A” team reviews and discusses each case, bringing their unique expertise to the table. Through consensus they conclude if findings are deemed actionable, lead to treatment recommendations, and are deemed informative.

According to Jan Egan, Ph.D., a Mayo Clinic research scientist and co-first author, the Genomic Tumor Board provided a translational platform to transform the practice.

“We brought together the unique perspectives of clinicians and laboratory scientists to drive treatment decisions and create patient focused research questions,” says Dr. Egan.

Jan Egan, Ph.D.

The Mayo Clinic Genomic Tumor Board engaged in patient case review to address limitations by considering genomic testing results, in addition to treatment options such as: surgery, ablation, radiation, new chemotherapy, or observation. Other benefits included facilitating collaboration between physicians and scientists to assist with target prioritization or consideration of alternate targets. It also provided a forum for teaching and consideration of alternative treatment options in complex cases. The Genomic Tumor Board contributed to the ongoing revolution of tumor genomic-based treatment in cancer, along with innovations in clinical trial design, technological innovations in big data management, and regulatory changes promoting data.

What are the barriers to delivery?

The study revealed these barriers to implementing genomics into cancer care:

  • Knowledge. Fewer than half of Mayo oncology faculty, fellows and advanced practitioners surveyed felt confident enough in their understanding of genomics to make treatment recommendations and explain it to patients. The majority sought input from colleagues or conducted a literature search when uncertain.
  • Access. Patients struggle with gaining access to the recommended therapy, pointing to drug access barriers that prevent optimal use of tumor genomic testing.
  • Cost. Out of pocket expenses and reimbursement varies by insurance company.

Looking ahead, researchers identified the importance of rapidly sharing insights gained from successful treatment to other clinicians and investigators. In addition, cross-institutional databases linking genomic profiles and treatment outcomes are needed given the rarity of specific abnormality/tumor combinations. Lastly, cost of tumor sequencing should be compared to the cost of treating with unselected therapies or enrolling in non-biomarker based clinical trials.

“We demonstrated treatment decisions driven by tumor genomic analysis can lead to significant clinical benefit in a minority of patients,” says Dr. Bryce.

Grant support

Center for Clinical and Translational Science grant UL1 TR000135, and the Mayo Clinic Center for Individualized Medicine.

Register to attend Individualizing Medicine 2017 and learn more about pharmacogenomics 

Join us to learn more about bringing precision medicine into practice at Individualizing Medicine 2017: Advancing Care Through Genomics.

The Mayo Clinic Center for Individualized Medicine is hosting the sixth annual genomics conference October 9–10, in Rochester, Minnesota.

Explore all conference offerings:

Mayo Clinic Center for Individualized Medicine is hosting the conference with support from the Jackson Family Foundation.

 

 

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