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Thu, Sep 20 6:00am · Gerstner awards boost research into hereditary cancer, Parkinson's disease

This article originally appeared on the Mayo Clinic Center for Individualized Medicine blog on August 27, 2018

Creating tools to detect cancer at an early stage and advancing research into the genetic links to Parkinson’s disease are focuses of the 2018 Gerstner Family Career Development Awards. This year’s winners are Niloy ‘Jewel’ Samadder, M.D., a gastroenterologist at Mayo’s Arizona campus whose research focuses on inherited cancer, and Fabienne Fiesel, Ph.D., a neurosciences investigator at Mayo’s Florida campus.

The Gerstner Family Career Development Awards in Individualized Medicine are given each year to early-stage investigators to advance individualized therapies. The award provides funding for research that furthers an individualized approach to predicting, preventing, treating and possibly someday curing disease. Another goal is to promote a specialized workforce capable of moving individualized medicine from discovery into patient care.

Niloy ‘Jewel’ Samadder, M.D.: Genetic testing as a screening tool

As a young physician-researcher, Dr. Samadder treated many young people with early onset cancers — the types that are passed down in families. These patients had a specific inherited gene that increased their chances of developing cancers throughout their body. People with inherited cancer genes often undergo an extensive battery of screening procedures every year including colonoscopy, endoscopy, ultrasounds and even preventative prophylactic surgeries. That inspired his current research to develop tools to non-invasively screen for multiple cancers for those at highest risk. Dr. Samadder envisions a tool similar to Cologuard®, a stool-based test developed at Mayo Clinic. His research will focus on designing a unique stool or blood test that could help detect a cancer at a very early stage anywhere in the body at a point when it is most curable.

Niloy “Jewel” Samadder, M.D.,

“Our goal is to develop a noninvasive, blood-based or stool-based tool that can be applied to hereditary cancers for patients who are at risk of multiple cancers,” says Dr. Samadder. “This is more likely to be accepted and completed by the patient. These tools could also make it easier for family members to be screened and learn who else is at a higher risk for hereditary cancer.”

Research shows that up to one in every five cases of cancer is linked to inherited mutations. As many as half of those cases are missed by current screening guidelines. Even after these patients are diagnosed with an inherited or genetic form of cancer, their screening can be complex and therefore, hard to follow. Additional tools may address that issue by providing new, less invasive screening options. For example, guidelines call for patients with Lynch syndrome, a genetic condition that comes with a high risk of colon, endometrial, ovary, stomach and other cancers – to have colonoscopies, and other time consuming screenings every year for the rest of their lives. Could a stool- or blood-based test to detect cancer be used as an alternative?

“It may not replace colonoscopy or other currently recommended tools completely in this high risk population, but instead of getting a colonoscopy every year, if this test is reasonably good, it could take the place of colonoscopy every other year,” says Dr. Samadder.

His research will focus on screening for inherited mutations in the following groups of cancers:

  • Colon
  • Uterine
  • Lynch syndrome
  • Breast/ovarian
  • BRCA syndrome
  • Duodenal

The Gerstner Award will allow him the time and opportunity to tap the expertise of others at Mayo Clinic in his research. This project has the potential to transform the care of patients with inherited forms of cancer and provide an individualized medicine approach to cancer prevention and early detection.

Fabienne Fiesel, Ph.D.: Seeking new therapies for Parkinson’s disease

Dr. Fiesel’s research seeks to discover new biomarkers — indicators of health and disease — with the ultimate goal of preventing, treating and curing Parkinson’s disease through precision medicine. Currently, there are approved therapies to treat the symptoms, but there is no known therapy or cure for the disease itself.

Her research centers on a fundamental cell biology pathway that links two genes involved in rare hereditary forms of Parkinson’s. Mutations in PINK1 and Parkin result in the accumulation of damaged mitochondria and lead to the death of the nerve cells, which causes loss of bodily function. Mitochondria are the powerhouse of a cell, acting like an energy source that keeps cells alive.

Fabienne Fiesel, Ph.D.

“There is evidence that mitochondrial damage is also linked to non-inherited forms of Parkinson’s and it is an early marker for several other (neurodegenerative) diseases,” says Dr. Fiesel. “A lot of research is being done to understand the biology of this pathway and to develop specific treatments to prevent mitochondrial damage.”

Dr. Fiesel’s team will perform deep molecular analysis, comparing cells with genetic mutations to cells of healthy people. She hopes to find a biomarker that will help to identify mitochondrial problems in Parkinson’s disease patients. This biomarker will be useful to test whether a specialized diet and exercise to improve the health of mitochondria, can have therapeutic benefits and whether specific therapeutic agents can be identified to correct or slow advancement of the problem.

“Hopefully someday we will be able to identify mitochondrial damage before a person has Parkinson’s or any other disease and before there is nerve damage. Then, maybe we could intervene with treatment before there is death of neurons and disease,” says Dr. Fiesel, “but this is only the beginning of our research.”

Dr. Fiesel’s project seeks to identify which Parkinson’s disease patients might be prime candidates for mitochondrial therapies when they are ready to be studied in clinical trials.





Mon, Sep 17 3:01pm · CIMCON18 -- How genomics discovery is transforming individualized care and the path forward

This article originally appeared on the Center for Individualized Medicine blog on Sept. 17, 2018.

Article by Sharon Rosen

Moderator Cathy Wurzer and Keith Stewart, M.B., Ch. B.

Mining information deeper than genomics, understanding factors linked to disease, analyzing big data, and addressing the challenges of bringing all this information together to advance patient care – these were some of the themes featured at the Individualizing Medicine Conference: Advancing Care through Genomics held in Rochester, Minnesota, Sept. 12-13, and sponsored by the Mayo Clinic Center for Individualized Medicine.

Keith Stewart, M.B., Ch.B., the Carlson and Nelson endowed director, Mayo Clinic Center for Individualized Medicine, opened the conference by explaining genomics discovery is moving rapidly and the conference gives a glimpse of the exciting research taking place along with how it is already improving patient care.

Here are some of the highlights from this year’s plenary speakers, all bringing their expertise to drive precision medicine forward.

The genomics landscape – from the Human Genome Project to next steps for future discovery

Eric Green, M.D., Ph.D.

Eric Green, M.D., Ph.D., director, National Human Genome Research Institute  at the National Institutes of Health (NIH) traced the advances of genomic testing since it was discovered three decades ago. Chief among them is the landmark completion of the Human Genome Project in 2003, which sequenced the first human genome. Since then, Dr. Green says, the cost of genomic sequencing has dropped by 1 million fold, and it can be done in weeks or days in some labs He also spotlighted key advancements:

  • Uncovering genetic links to cancer
  • Understanding drug-gene interactions through pharmacogenomics
  • Using genomic testing to identify more than 4,000 rare genetic diseases
  • Advancing prenatal care so the health of the baby can be assessed through genetic testing from the mother’s blood, rather than with invasive tests like amniocentesis

Now genomic testing is moving from the research setting into clinical practice. Dr. Green and his team forecast that by 2022, more than 80 percent of genetic testing will take place in the health care system. This trend is one of many factors Dr. Green and his team are considering as they develop a 2020 strategic plan for advancing genomics, gathering input from the broad scientific, health care and patient communities.

Dr. Green also highlighted the National Institutes of Health All of Us Research Program, an unprecedented national research  program that kicked off in May.  All of Us  is enrolling a million people into a research cohort to advance an individualized approach to managing health and disease. Mayo Clinic is home of the biobank that will store biospecimens for the All of Us Research Program.  As of August 2018, Mayo had stored nearly 1.7 million samples from more than 57,000 participants.

Moving pharmacogenomics into daily clinical care

Richard Weinshilboum, M.D.

According to Richard Weinshilboum, M.D., pharmacogenomics is the first area of precision medicine that will be integrated into patient care daily, and predicts that it will, eventually touch every patient everywhere.

Dr. Weinshilboum is co-director of the Mayo Clinic Center for Individualized Medicine Pharmacogenomics Program and a pioneer in the field of pharmacogenomics, which explores how a person’s genetic characteristics affect their response to medications.

At the conference, Dr. Weinshilboum shared the promise and challenges of implementing pharmacogenomics into daily clinical practice. He highlighted Mayo’s RIGHT 10K study, which will add preemptive pharmacogenomics test results for 10,000 Mayo Clinic Biobank patients into their electronic health record.

The goal is to understand how  having this genetic information available at the point of care may help improve care.  The idea is that this information will guide health care providers to identify medications and/or make dose adjustments that are compatible with a patient’s genetic makeup, maximizing the therapy benefit and reducing harmful side effects.

Uncovering the mechanisms driving disease

Manolis Kellis, Ph.D.

Manolis Kellis, Ph.D. is going beyond genomics to understand the processes driving disease. Dr. Kellis, a computational biologist at Massachusetts Institute of Technology (MIT) and the Broad Institute, and his team have developed maps to understand how genetic variations and other biological and molecular processes contribute to many diseases, including heart disease, Alzheimer’s, cancer and obesity.

This groundbreaking approach has uncovered some surprising results. For example, Dr. Kellis and his team found that the strongest genetic association with obesity acts via a master switch controlling energy storage and expenditure, rather than through the control of appetite in the brain. This finding suggests that there is more to controlling weight than watching your diet and getting regular exercise.

Mining biobank and electronic health record data to uncover genetic links to common diseases

Nancy Cox, Ph.D.

While it is exciting to have additional information about patients – their genomic test results, biological data and health history, how can researchers interpret that information so that it can improve a patient’s care?

Nancy Cox, Ph.D. and her team are addressing this challenge with computer models. Dr. Cox, director, Vanderbilt University Genetics Institute and Division of Genetic Medicine, is using these tools to analyze genetic test results from biobank participants, along with data from their electronic health records to better understand a patient’s risk for disease.

As Cox explained, the advantage of this approach is it allows researchers to look across all of the diagnoses associated with a specific gene at the same time, rather than the traditional approach of focusing on one disease. This uncovers conditions or symptoms that may help predict disease, prompting earlier screening and treatment. They’ve developed a publically available catalog of these associations, which include not only genomic but other biological and environmental factors that can help predict disease.

Imaging biomarkers to predict disease

Gabriel Krestin, M.D., Ph.D.

Gabriel Krestin, M.D., Ph.D. is also developing models to predict disease and has been a leader in combining imaging methods with genomic, biological and environmental data to identify subtle changes linked to disease risk.

Using artificial intelligence to analyze data from large-scale population studies of healthy individuals, he and his team have identified imaging biomarkers to predict complex diseases such as dementia and Alzheimer’s.

Their findings are being used to help detect and treat disease sooner.

Dr. Krestin is chairman, Department of Radiology and Nuclear Medicine at Erasmus MC, University Medical Center Rotterdam, in the Netherlands.

Michael Berger, Ph.D.

MSK-IMPACT – large scale genomic testing to guide cancer care

Michael Berger, Ph.D. has made great strides in expanding the search for genetic links to cancer. Dr. Berger, a geneticist at Memorial Sloan Kettering (MSK), and his team developed MSK-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), a genetic test that looks across 468 genes associated with both rare and common cancers.

By using MSK-IMPACT to screen more than 20,000 MSK patients with advanced cancer, Dr. Berger has created the largest gene panel database.

Berger highlighted how this testing has changed the course of treatment for patients. For example, MSK-IMPACT testing revealed that a woman previously thought to have metastatic breast cancer actually had cancer that originated in her lungs. As a result, her treatment was changed from hormone therapy to the appropriate chemotherapy.

Test results are also helping direct patients to clinical trials based on the genetic characteristics of a patient’s tumor, rather than where the tumor originated.

CAR T-cell therapy – reengineering immune cells to fight cancer

Yi Lin, M.D., Ph.D.

Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is a new immunotherapy that reengineers a patient’s own immune cells to create a  living drug that recognizes and fights a patient’s cancer. The therapy is currently approved to treat patients with B-cell non-Hodgkin’s lymphoma and B-cell acute lymphocytic leukemia (ALL) who have not responded to standard therapy.

Yi Lin, M.D., Ph.D., a hematologist at Mayo Clinic’s campus in Rochester, Minnesota, and chair of the Cellular Therapeutics Cross-Disciplinary Group in the Mayo Clinic Cancer Center, shared promising clinical trial results where the majority of patients responded to this new, individualized treatment. She also explained that it is most appropriate for patients whose disease has stabilized and who can handle the range of side effects that may come with this treatment.

Next steps – expand collaboration, build evidence and boost genomic literacy

Heidi Rehm, Ph.D.

Heidi Rehm, Ph.D., wrapped up the conference  with a presentation on collaboration and data standards that are keys to improving the rate of diagnosing rare, genetic diseases. Dr. Rehm has championed many efforts to discover and share disease-related variants in order to move genomics into clinical care.

Dr. Rehm is a geneticist and genomic medicine researcher at the Broad Institute Chief Genomics Officer at Massachusetts’s General Hospital and Professor of Pathology and Harvard Medical School.

Timothy Curry, M.D., Ph.D. and Cathy Wurzer

So what are the next steps in genomics?

“We need to expand these collaborations to build the critical evidence needed to translate genomics into better prevention, screening and treatment for patients. We’re also working to boost genomic literacy so that physicians and patients understand how genomics,  along with other clinical information, can enhance patient care ,” says Timothy Curry, M.D., Ph.D., director, Mayo Clinic Center for Individualized Medicine Education Program.

More conference highlights

Up next – pharmacogenomics for the modern health care team

Mark your calendar and plan to join us at Drugs and Genes: Pharmacogenomics for the Modern Health Care Team 2018 in Scottsdale, Arizona from Nov. 30 to Dec. 1, 2018.

Keep the conversations going

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Thu, Aug 23 8:00am · Using the body to recognize and attack cancer

This article originally appeared in the Center for Individualized Medicine blog on July 23, 2018

For as long as he can remember, Saad Kenderian, M.B., Ch.B., wanted to be a physician. Nothing could blunt his resolve –not even when improvised explosive devices, bombs and trappings of war put the medical school in his native Baghdad, Iraq, on a brief hiatus. It is with that same determination he leads Mayo Clinic’s research into chimeric antigen receptor (CAR) T-cell therapy, which unleashes the immune system to attack cancer.

Saad Kenderian, M.B., Ch.B.

“With CAR T, we are on the verge of discovering the potential of immune cells. The results that we are seeing are truly unprecedented, especially in B-cell leukemias and lymphomas. Some patients who really have no other hope are going into complete remission,” says Dr. Kenderian.

With support from the Mayo Clinic Center for Individualized Medicine, Dr. Kenderian’ s team is investigating ways to expand CAR T-cell therapy beyond blood cancers to solid tumors and to autoimmune diseases like colitis.

Fighting cancer with genetically engineering cells

CAR T-cell therapy seeks to harness the power of the immune system by genetically modifying cells, equipping them with power to kill cancer. These synthetic cells act like a living drug that uses the body’s defense system to fight disease.

“This is a prime example of individualized immune therapy. Immune system T-cells are taken from each patient and engineered with an artificial protein that supercharges them to recognize and attack cancer. A large number of these cells are then injected back into the body. It’s a therapy shaped to each patient,” Dr. Kenderian says.

CAR T-cell therapy may be used on lymphoma and leukemia patients whose cancer has returned twice and no longer responds to standard therapy. Studies are underway to investigate whether it would be beneficial to start CAR T-cell therapy earlier.

One focus of Dr. Kenderian’s research is the “next generation” of CAR T-cell therapy. The research is looking for treatment with fewer side effects, lower cost, and use on solid tumors.

“The first challenge with that is unlike blood cancers, there is no unique protein or marker on the cancer cells for the CAR T-cells to attack. The second challenge is that solid tumors have a unique environment that is able to shut down the CAR T-cells. We hope to advance our understanding about this within the next five years,” he said

Fascinated with the immune system

Part of Dr. Kenderian’s dream was to practice medicine in the United States. After completing his residency at Michigan State University McLaren Hospital, he came to Mayo Clinic for a fellowship in hematology and oncology. It was during that time he grew fascinated with the power of the immune system and the potential that a patient’s body could fight disease.

“Tapping the immune system is perhaps one of the only therapeutic strategies that we can talk about as a potential cure (for cancer),” he says.

As part of his fellowship, Dr. Kenderian studied under the pioneers of CAR T-cell therapy at the University of Pennsylvania. He returned in 2016 to help establish the CAR T therapy program at Mayo Clinic.

Mayo is a leader in CAR T-cell therapy

Mayo Clinic is now one of a select few medical centers in the United States to offer CAR T-cell therapy in a clinical setting.

“Mayo Clinic is unique in this setting, because we have the clinical infrastructure to deliver the CAR T-cell therapy. And we have a solid interdisciplinary collaboration between basic science, clinical sciences and translational approaches to bring these discoveries to the clinic,” he says.

CAR T-cell therapy will be showcased at this year’s Individualizing Medicine Conference.

Sponsored by the Mayo Clinic Center for Individualized Medicine, the conference will be held on Sept. 12-13 at the Mayo Civic Center in Rochester.  You can register to attend here.

Join the conversation

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.


Thu, Aug 9 6:00am · Using CSI-type technology to unravel the source of bacteria

This article originally appeared on the Center for Individualized Medicine blog on May 28, 2018.

Mayo Clinic laboratory workers have a new tool to perform high tech genetic sleuthing for the source of stubborn, sometimes life-threatening bacteria. Bacterial whole genome sequencing can trace individual isolates of bacteria such as Staphylococcus aureus, also known as Staph aureus, to determine if an outbreak is occurring. This common bacterium that has plagued health care facilities, nursing homes, neonatal intensive care units and sports teams can lead to serious infections and can be resistant to some available antibiotics.

Robin Patel, M.D.

“If we have two or more people infected with the same type of bacterium, the question sometimes arises as to whether they got the organisms from one another or a shared source. The answer to this question can shape an approach to limit further spread,” says Robin Patel, M.D., a clinical microbiologist with Mayo Clinic Department of Laboratory Medicine and Pathology. “Or, a patient might have a bacterial infection and later a second infection with the same type of bacterium. Whole genome sequencing can determine whether the patient picked up a new ‘version’ of the bacterium or if the old one never went away. This can matter for management of that patient.”

Staph aureus bacteria are a leading cause of skin and underlying infections, such as boils, abscesses and cellulitis. Often this type of infection is not serious. However, the same organism-type can cause more serious infections, such as bone or joint infections. Sometimes Staph aureus can spread to the bloodstream and become life threatening.

In the past, getting to the source of outbreaks and transmission was tricky. Prior to bacterial whole genome sequencing, lab workers had to rely on a type of molecular testing, called pulsed-field gel electrophoresis, that was tedious, difficult to analyze and produced only a fraction of the information that DNA sequencing does.

Nicholas Chia, Ph.D.

“It is important to develop tests that can distinguish how individual bacteria are related to one another and to understand and control the spread of bacterial infections,” says Nicholas Chia, Ph.D., assistant director of the Center for Individualized Medicine Microbiome Program.

Mayo Clinic Center for Individualized Medicine is working with the Mayo Clinic Department of Laboratory Medicine and Pathology to bring to the medical practice new testing methods that look at the entire genomes of human pathogenic bacteria.

“With microbial whole genome sequencing, we can discover all there is to possibly know about an organism. It is cutting edge technology that’s a little like CSI (crime scene investigation) in a way. We are providing information to assess relatedness, which will in turn direct interventions to interrupt transmission,” says Dr. Patel.

Research has shown that whole genome sequencing can help track the source of the stubborn superbugs such as methicillin-resistant Staphylococcus aureus, or MRSA, outbreaks that have been reported in high school, college and professional sports teams, in addition to in health care facilities. Many times, MRSA infection is spread via turf, locker room towels or personal contact between athletes. Whole genome sequencing can confirm the presence of an outbreak.

“Examining the entire bacterial genome, we will, in the near future, be able to identify resistance genes and mutations, therefore defining which antibiotics are going to be active. Our early research indicates that we can use whole genome sequencing to inform drug selection and therefore how that patient should be treated. It is so new, we’ve elected to look at this application separately from the strain relatedness testing approach we are currently performing,” says Dr. Patel.

Mayo Clinic is one of the first medical centers in the United States to routinely perform whole genome sequencing of Staph aureus bacteria in its clinical labs. The tests for this and other bacteria are available to other health care facilities through Mayo Medical Laboratories.

Additional research can be found here.

Join the conversation

For more information on the Mayo Clinic Center for Individualized Medicine, and how it is transforming care through the discovery, translation and application of precision medicine research, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Save the date for this year’s Individualizing Medicine Conference. It will be held Sept. 12-13, 2018 in Rochester, Minnesota.

Thu, Jul 19 8:00am · A clearer picture: new imaging technologies advance diagnosis, individualized care

New imaging technologies are advancing diagnosis and individualizing care. Imaging tests – such as a CT scan or MRI – are essential tools that health care providers use to answer complex and challenging questions.

Gabriel Krestin, M.D., Ph.D.

Gabriel Krestin, M.D., Ph.D., a radiologist and researcher, is at the forefront of new efforts to apply cutting edge imaging technologies that can detect subtle biological and molecular changes to more accurately diagnose and treat disease. At this year’s Individualizing Medicine Conference: Advancing Care through Genomics, Dr. Krestin will discuss his work on integrating new imaging methods to identify objective, quantitative, and standardized features available in digital images – called imaging biomarkers – that can be important to predict complex diseases, their outcome and monitor treatment. The conference will be held September 12 and 13 at the Mayo Civic Center.

New techniques offer a better view of disease

Historically, imaging has been used by physicians to visualize anatomy without even picking up a scalpel. Within the past several decades new imaging methods are providing a better look at the size, location and biological characteristics of normal and disease processes within the body.

“New imaging techniques offer important information about the physiology, organ function, and biological and molecular functions, allowing us to predict disease long before symptoms appear,” explains Dr. Krestin.


Sponsored by the Brandt Family Scholars Fund, the Early Career Investigators in Precision Medicine Scholarship Program is looking for early-career investigators with an interest in individualized medicine. Awardees will present their research-based or challenging case as a poster and/or concurrent platform presentation at the Individualizing Medicine Conference.

Deadline to apply is July 30 at Abstract Scorecard.

The Brandt Family Scholars Fund seeks to encourage and support early career investigators in precision medicine discovery or translation. See the Individualized Medicine Blog for past awardee information.

These imaging biomarkers are playing a key role in precision medicine research and practice, helping to reveal subtle differences that can indicate the best individualized approach for choosing the right therapy.

“This “deep imaging phenotyping” is at the basis of the emerging field of radiomics, allowing us to play an increasing role in prediction of disease, of outcomes and of therapy response. Using aartificial intelligence and computational methods, we can integrate imaging data with genomic, clinical and environmental information to provide new knowledge to guide patient care. The key to the success of this new ‘data driven medicine’ approach is collaboration among multiple specialists to interpret these results and then develop individualized treatment plans for patients,” says Dr. Krestin.

An opportunity to learn from a leader

Kiaran McGee, Ph.D., director of the Center for Individualized Medicine Imaging Biomarker Discovery Program, notes that Dr. Krestin’s research has focused on imaging of abdominal organs and cardio-vascular diseases, molecular imaging and population imaging.

Kiaran McGee, Ph.D.

“Dr. Krestin has worked at many leading academic medical institutions and serves on many advisory boards, allowing him to have his finger on the pulse of advances in radiological imaging and how these new techniques can be applied to improve personalized patient care,” says Dr. McGee.

Dr. Krestin is a professor of Radiology and Chairman of the Department of Radiology and Nuclear Medicine at Erasmus MC, University Medical Center Rotterdam, in the Netherlands. In 2017, he was elected to the National Academy of Science, Engineering and Medicine (US). He has authored more than 400 publications and over 70 book chapters.


Register now for the Individualizing Medicine Conference, Sept. 12-13, 2018, in Rochester, Minnesota.

Thu, Jul 12 6:00am · Arresting melanoma's molecular drivers

This post originally appeared on the Center for Individualized Medicine blog on May 15, 2018.

Article by Barbara Toman

Melanoma, the skin cancer often associated with sun exposure, is on the rise and has no reliable cure. Mayo Clinic is at the forefront of efforts aimed at increasing early detection and treatment of this aggressive disease.

The Center for Individualized Medicine (CIM) is unravelling the complex behavior of melanoma at the molecular level— to allow for treatment that better targets an individual’s disease.

Aleksander Sekulic, M.D., Ph.D.

“All melanomas are not the same. The ability to understand what may be driving different subsets of melanoma at the molecular level allows us to use treatment appropriate for a particular patient,” says Aleksander Sekulic, M.D., Ph.D., a dermatologist in the Cancer Center and assistant CIM director at Mayo Clinic in Phoenix, Arizona.

About 90,000 people are diagnosed with melanoma and more than 9,000 people die from the disease in the United States every year, according to the American Cancer Society. The incidence has been rising for the past 30 years, especially among young people.

“If melanoma isn’t caught very early, it tends to spread. ‘Early’ means melanoma on the skin with a thickness of less than 1 millimeter — which is essentially three grains of table salt,” Dr. Sekulic says. “We need to develop better therapies because we know that even recent advances that are nothing short of miracles will work only in a subset of patients, not all patients.”

One recent advance is the development of immunotherapies — medications that stimulate a person’s immune system to recognize and destroy cancer cells more effectively — which can benefit some people with melanoma. Another advance involves the discovery that about half of people with melanoma have an abnormal version of a gene known as BRAF.

“The BRAF mutation essentially acts like a switch that is stuck in the ‘on’ position and promotes abnormal cell growth,” Dr. Sekulic says. “Therapies that turn off the mutated BRAF molecule — cutting the growth signal for cancer — have significant efficacy in people whose melanoma harbors the BRAF mutation.”

But those medications, known as BRAF inhibitors, can actually worsen melanoma in patients without the BRAF mutation. Currently, treatment options are very limited for people whose melanoma doesn’t harbor the BRAF mutation and who don’t respond to immunotherapies.

To pave the way for new treatments, Mayo Clinic is involved in a large trial aimed at identifying additional molecular drivers of melanoma. The trial is gathering genetic information from people with melanoma who lack the BRAF mutation.

“We want to merge information about other genetic alterations that might be present in those individuals’ cancers with our knowledge of drugs that are currently available. The goal is to identify a target we haven’t anticipated in melanoma that might respond to an existing medication,” Dr. Sekulic says.

The researchers are discovering that for now, their knowledge of melanoma’s molecular drivers is outpacing drug development. “There is a bottleneck — we have learned much more about melanoma than we can act on,” Dr. Sekulic says. “But the drug development is rapidly catching up.”

He notes that individualized treatment of diseases was made possible by the sequencing of the human genome, which occurred just 15 years ago. “I would guess that within 10 years we will be in a very different place than we are now in terms of melanoma treatment,” Dr. Sekulic says.

Liquid biopsy for the BRAF mutation

Mayo Medical Laboratories has developed a “liquid biopsy” to detect the BRAF mutation in a blood sample. Assessing BRAF mutation status in people with melanoma typically involves removing cancerous tissue for testing in the laboratory.

“This new technology provides an opportunity to limit invasive tissue biopsies and get the necessary information from a simple blood test,” says Minetta C. Liu, M.D., an oncologist at Mayo Clinic, who helped develop the test. “In an individual with newly diagnosed melanoma that’s progressing rapidly, we may not have time to arrange a tissue biopsy and wait several days for the tissue results. Now, we can reliably determine BRAF mutation status through that blood draw within a day.”

Further work is underway to determine how best to use the test clinically. One possibility is using the blood test to assess the effectiveness of treatment in people with BRAF mutant melanoma.

Minetta Liu, M.D.

“Gradual disappearance of a detectable BRAF mutation in the blood suggests that the cancer cells are responding, and the patient is benefitting from current therapy. This seems intuitive, but we have to prove it,” Dr. Liu says. “It’s such a rapidly evolving field. We’re working to make this blood test part of clinical guidelines to take better care of patients.”

Lessons from down under

Dr. Sekulic stresses that melanoma is largely preventable. The major risk factor is exposure to ultraviolet (UV) rays, and the major source of UV rays is sunlight.

“The most efficient way to reduce the burden of melanoma is sun protection,” Dr. Sekulic says. “Previous UV exposure, especially sunburns early in life, can make a dramatic difference in a person’s risk for melanoma.”

Australia has curbed its incidence of melanoma through campaigns advocating sun-protective clothing, sunscreen and sun avoidance. “These are very simple methods,” Dr. Sekulic says. “Protecting our children from UV rays is where we ultimately will have the largest impact on melanoma.”

Join the conversation

For more information on the Mayo Clinic Center for Individualized Medicine, visit our blogFacebookLinkedIn or Twitter at @MayoClinicCIM.

Learn more about the latest clinical applications of precision medicine at this year’s Individualizing Medicine Conference. It will be held Sept. 12-13, 2018.

Fri, Jun 22 3:47pm · Be the early bird! Register now for the 2018 Individualizing Medicine Conference

Mayo Clinic Center for Individualized Medicine  is hosting the Individualizing Medicine Conference (#CIMCON18), Sept. 12-13, 2018, in Rochester, Minnesota.

#CIMCON18 brings together experts from Mayo Clinic and around the world to discuss how the latest discoveries in precision medicine can be applied to improve patient care.

Register today for the conference and save $100

Use code EB100 before June 29!

In her plenary presentation at #CIMCON18, Nancy Cox, Ph.D., will explain how biobank research offers a unique opportunity to explore links between multiple diseases.

There is no single gene that causes diabetes, bipolar disorder or Alzheimer’s disease, but there are genes linked to conditions that may occur before a patient eventually develops these disorders. What if researchers could identify individuals whose genetic makeup puts them at risk for developing disease so that physicians could intervene sooner and provide more effective treatment?

These are the questions that Nancy Cox, Ph.D. and her research team at Vanderbilt University are asking as they analyze tissue samples and electronic medical record data for thousands of biobank participants in order to better understand genetic risks for many common diseases. As Director of both the Vanderbilt Genetics Institute and Division of Genetic Medicine, Dr. Cox studies the individual and collective genetic and health information of biobank participants.

Read more about Dr. Cox and her research.

For a complete schedule and list of speakers, visit the conference website.

Follow the latest news related to the conference on the Center for Individualized Medicine blogFacebookLinkedIn or Twitter at @MayoClinicCIM and use the hashtag #CIMCON18.


Tue, Jun 12 8:00am · Genetic testing to enhance multiple myeloma treatment

This article originally appeared on the Center for Individualized Medicine blog on March 6, 2018

Article by Barbara Toman

Multiple myeloma is the second most common blood cancer, but most people haven’t heard of it until they or someone they know is diagnosed with the disease. March is Myeloma Action Month — a time to focus attention on the fight against multiple myeloma.

Mayo Clinic is making significant advances with an individualized medicine approach. In recent years, Mayo researchers and others have uncovered a wealth of information about the genetic mutations that help multiple myeloma cells survive and multiply. Now, Mayo Clinic has translated those discoveries into clinical testing to personalize care.

Keith Stewart, M.B., Ch.B.

“Multiple myeloma has some of the most advanced genomic information available among all cancers. We have condensed that large genomic database into a test panel to detect genetic mutations that have relevance to prognosis and to optimal drug therapies for individual patients,” says Keith Stewart, M.B., Ch.B., a multiple myeloma specialist and director of the Mayo Clinic Center for Individualized Medicine (CIM).

The test panel, available through Mayo Medical Laboratories, uses next-generation sequencing to pinpoint genetic mutations within an individual’s tumor. The mutations make an individual likelier to respond to — or likelier to resist — the effects of a particular drug.

“The panel will detect mutations that have relevance to prognosis, to drug sensitivity and resistance, and to the different types of myeloma that might be present in the patient’s sample,” Dr. Stewart says. “That helps us understand whether we need to raise the intensity of the therapy, whether we’re able to eradicate certain elements of the tumor over time, whether drug resistance is emerging and — critically — helps us to identify precision therapies when certain mutations are present.”

Multiple myeloma cells have the ability to evolve rapidly, changing their genetic profiles over time. Certain genetic subtypes of multiple myeloma respond poorly to treatment. One type of chromosome abnormality linked to multiple myeloma is a mismatching of chromosome parts known as chromosomal translocation.

“In the next few months, the test panel will also be able to tell us the chromosomal translocations that are present in the tumor,” Dr. Stewart says. “We can already do that in the research laboratory, and we’ll soon translate that to the clinical lab.”

Moving the ball forward

The individualized-medicine approach to multiple myeloma has yielded a major development in precision therapy. New treatments have recently been found to be effective for multiple myeloma involving a certain chromosomal translocation.

Mayo Clinic is working towards other breakthroughs, building on its history as a global leader in multiple myeloma. That history dates back to the 1960s and the work of Robert A. Kyle, M.D., who continues to be an active researcher at Mayo Clinic.

“We’re building on Dr. Kyle’s long tradition,” Dr. Stewart says. “We have a very deep and strong myeloma group, both clinically and in the research domain, along with our strong presence in individualized medicine. We’ve also been blessed by our collaboration with the Multiple Myeloma Research Foundation. Mayo is working with the Foundation on one of the largest genomic studies of any cancer that’s ever been done.”

As a major clinical and research center, with a global patient population, Mayo Clinic has compiled a significant database on multiple myeloma. “Over the past 50 years, we have collected information on patients as well as 45,000 to 50,000 patient samples,” Dr. Stewart says.

“We’ve made great progress over the past five years in developing an individualized medicine approach to treating multiple myeloma,” he adds. “Our commitment to patient care, along with a plethora of clinical trials and investigative laboratory work, will allow us to continue to move the ball forward.”

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Learn more about the latest clinical applications of precision medicine at this year’s Individualizing Medicine Conference. It will be held Sept. 12-13, 2018.

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