Tag Archives: genetic

New Personalized Medicine Products Signal Progress for Patients

Guest post by Edward Abrahams, PhD; President, Personalized Medicine Coalition

Edward AbrahamsThe approvals of new treatments for two different types of cancer indicate that we are making significant progress in personalized medicine. Although the U.S. Food and Drug Administration (FDA) could further define a more transparent and predictable regulatory environment for personalized medicine products, the agency is clearly serious about personalized medicine. In August it cleared Xalkori® (crizotinib), which targets a rare form of lung cancer, ahead of its own priority six-month review goal and Zelboraf® (vemurafenib), which treats patients with melanoma also well ahead of schedule.

These combination products represent a harbinger of the future of medicine. By applying new genetic understanding of tumors to target treatments, drug and diagnostic companies working together are able to develop drugs that are safer and more effective, offering hope to cancer patients where none existed.

In the case of Xalkori®, Pfizer and Abbott Molecular co-developed the drug and a companion diagnostic test (Vysis ALK Break Apart FISH Probe Kit) to identify the subset of patients who are most likely to respond to the drug.  Around five percent of patients diagnosed with non-small cell lung cancer, the most common form of the disease, have tumors with an anaplastic lymphoma kinase (ALK) gene defect that responds to the drug – about 6,000 patients per year in the United States.  Xalkori® works by blocking proteins produced by the abnormal ALK gene.  It is the first lung cancer treatment developed and approved with a diagnostic test.

Stafford O’Kelly, Abbott Molecular Vice President and President Molecular Diagnostics, noted, “[This collaboration] marks a breakthrough in the advancement of personalized medicine…that will help a subset of lung cancer patients get treatment tailored to their unique genetic profile.”

Also recently approved is a targeted therapy to treat melanoma – the deadliest form of skin cancer.  Zelboraf® is indicated for treatment of patients with melanoma whose tumors express a gene mutation called BRAF V600E, which the drug blocks.  Approved with a diagnostic test (cobas® 4800 BRAF V600 Mutation Test) that determines which patients carry the mutation, the drug was clinically effective in 50 percent of these patients.

These new models for collaborative research and development of treatments are yielding positive results. They should keep us focused on the emerging field of personalized medicine and its promise to deliver the right treatment to the right patient with improved diagnosis, more efficient drugs, and better medical outcomes.

Personalized Health Care: The Key to Meaningful Healthcare Reform

Guest post by Ralph Snyderman, M.D., Chancellor Emeritus and James B. Duke Professor of Medicine, Duke University and Chairman, Proventys, Inc.

Ralph Snyderman


The practice of medicine is currently in the early stages of a transformation made capable by major advances in science, technology, and know-how which is enabling personalized health care.  Genomics, proteomics, systems biology, informatics, micro and nano-processing, etc., are creating capabilities that are already revolutionizing health care. Whereas the sciences of the 1900s facilitated the understanding of disease and supported the goal to “find it and fix it,” the new sciences are enabling the personalization, prediction, and prevention of many chronic diseases.  Development of disease is based on an individual’s inherited baseline susceptibilities which are modified by exposure to environmental factors.  While previous approaches to medicine have been focused on reversing disease events, emerging approaches are dynamic and recognize that diseases develop over time and their development can often be modified or prevented.

Recognizing the dynamic basis of disease development has profound implications for the practice of medicine and indicates that care should be proactive and account for each individual’s unique characteristics. Moreover, understanding the dynamic nature of disease development envisions a healthcare approach where each individual’s susceptibility or resistance to disease is quantified and tracked over time to determine whether a disease is progressing or regressing.  With the ability to assess an individual’s disease susceptibility and identify factors for tracking disease progression, a strategic approach to health care can be developed to enhance health and minimize disease — one that is personalized, predictive, preventive, and engages the individual in their care; e.g., “personalized health care.”  This latter point is critical as an individual’s behavior is often far more important for preventing or enhancing disease development than any specific therapeutic intervention by a healthcare provider.

Personalized health care applies the concepts of systems biology, personalized, predictive, preventive, and participatory care (e.g., P4 Medicine,) and health planning to customize care across the continuum from health promotion to disease treatment.  Personalized health care is based on the premise that each individual is born with a unique genetic inheritance and that health or disease is a consequence of how this background is modified by environmental exposure over time.  Even though a great deal of an individual’s genome is shared by all, variations result in each person having unique susceptibilities or resistances to various diseases as well as shared and unique strengths for enhancing health and fitness. Since an individual’s current clinical status can be assessed and their risks for disease evaluated, the approach to health care can be changed from identifying and responding to disease to a strategic approach where disease risks are quantified and, where possible, prevented by personalized health planning. If diseases develop, they are identified early and characterized mechanistically in order to treat them appropriately, thereby minimizing their adverse impacts. 

Personalized health care is based on the scientific foundation that recognizes the dynamic relationship between genetic inheritance, environmental exposures, and systems biology.  Wherever possible, the best predictive tools are used to identify each individual’s health risks, track their risks over time, identify the specific mechanism of their disease, and determine the best therapeutic approaches directed to their needs.  Care is mediated through health planning and coordinated care.  Personalized health care can be used to enhance health, prevent disease, track its development, intervene early, and manage disease most effectively if it occurs. 

The personalized health plan is fundamental to personalized health planning.  It is the instrument used to implement an individual’s care over a specified time. For primary care, the individual’s current health status is evaluated using the best appropriate clinical technologies along with the best available health risk technologies.  Depending on the individual’s health status, their degree of risks for any given disease, their age, and other factors, the patient and their provider would develop objectives to improve health and prevent disease in partnership with a coordinated health system.  Tracking factors would be identified to monitor progression or regression of disease or perhaps to monitor the onset of disease.   These factors could be as simple as weight, BMI, measurement of blood pressure or biomarkers, including the broad array of emerging personalized medicine tools.  The personalized health plan can also be used for secondary prevention or disease management where it is focused on the patient’s specific clinical condition defined mechanistically by using personalized medicine tools.  Characterizing disease mechanistically rather than phenotypically allows the introduction of more personalized approaches for tracking disease progress and for targeting the most appropriate therapeutic interventions.  For an increasing number of applications, therapies targeted at specific diseases can be identified with companion diagnostics thus enabling treatment tailored to the individual’s needs. 

In conclusion, science and technology are creating new understandings of health and disease as well as capabilities to predict, prevent, and treat disease based on the individual’s needs.  Personalized health care is the application of clinical know-how and personalized medicine technologies to assess an individual’s health risks, track disease progression or regression, and treat it most appropriately when it occurs.  Personalized health care is a means to focus the increasing capabilities of personalized medicine on a coherent model of health prevention and disease avoidance.  Personalized health care can begin today and will improve care and facilitate the development and expansion of new technologies.


Genetics, Genomics and Personalized Medicine

Post by Kevin Sweet, Human Genetics, The Ohio State University Center for Personalized Health Care

Kevin Sweet

Over the next decade, the use of genetic/genomic approaches for common and rare disease risk prediction will become commonplace. Whole genome sequencing and other technological innovations will drive these developments. Application of this predictive genetic risk information in the clinical setting, one component of P4 Medicine, is essential if one is to tailor personalized disease management and prevention approaches, and to allow active patient participation in the process.
While some predictive genetic tests may lend themselves to relatively straightforward approaches and interpretation, others will be masked by the complexities of molecular biology, and interpretation will not be as clear. All disease is complex disease, and knowing just one gene variant for any given disease may not be enough. Other gene variants, silent mutations that disrupt gene function, copy number variants and epigenetic factors are only a few of the additional influences that may come into play.  Family history and non-genetic (environmental, lifestyle) risk factors must also be taken into account.  Indeed, one of the biggest challenges facing researchers in the field of personalized (P4) medicine today is determining exactly how the critical genetic and non-genetic factors (both risk and protective factors) interact to influence one’s risk for any given disease.
Another huge challenge will be to provide healthcare practitioners with the point of care tools and resources to educate (or refresh) themselves on the basic molecular principles that underlie genetic/genomic information, and allow them to critically appraise and utilize the new information coming down the road. This point was driven home in the 2009 “Scientific Foundations for Future Physicians,” report sponsored by the Association of American Medical Colleges and the Howard Hughes Medical Institute (http://www.hhmi.org/grants/pdf/08-209_AAMC-HHMI_report.pdf).
This report states that physicians should be able to: “Use the principles of genetic transmission, molecular biology of the human genome, and population genetics to infer and calculate risk of disease, to institute an action plan to mitigate this risk, to obtain and interpret family history and ancestry data, to order genetic tests, to guide therapeutic decision-making, and to assess patient risk.” Given the more than 800,000 physicians in current practice, the task at hand is large. While genetic professionals will continue to assist in educating practicing physicians, medical students and other members of the healthcare team (nurses, physician assistants, pharmacists, etc), much of the impetus for incorporating this information into everyday practice will have to come from the medical professionals themselves.
It is for this reason that a colleague and I recently published a book entitled, “The Busy Physician’s Guide To Genetics, Genomics and Personalized Medicine.” The book was designed to help current practicing physicians and the entire healthcare team better understand and apply principles of genetic and genomic medicine into everyday practice. It provides a thorough review of the basic molecular biology one needs in order to understand the genetic variability that underlies personalized medicine. As family history remains the gold standard for disease risk assessment, we also provide guidance on how to collect and use family history, and valuable web-based assessment tools to actively involve the patient in the process.
We provide extensive review and concrete examples of the genetic tests available today, and the basis of the discoveries that will give rise to the next wave of personalized medicine tests. We hope this resource will help the physician healthcare team become more comfortable applying concepts like genetic variation in the clinical setting, for individual disease risk assessment and pharmacogenomics. Of equal importance, we hope this provides a foundation so one can critically appraise the new scientific information that will be available in increasing abundance in this field in the not too distant future.

The Ghost of Personalized Medicine

Captured by The Scientist

The US Food and Drug Administration recommends that doctors genotype patients before prescribing more than 70 commonly-used medications for specific genetic biomarkers. These tests, the agency suggests, can help physicians identify those in which the drug is less efficacious, poorly metabolized, or dangerous. But medicine is still far from a day when drugs and treatment regimes are fitted precisely to a patient’s genomic profile.

According to a 2008 survey conducted by the American Medical Association (AMA) and Medco Research Institute, even though 98 percent of physicians agreed that the genetic profiles of their patients may influence drug therapy, only 10 percent believed they were adequately informed about how to test their patients for biomarkers that may predict the safety and/or efficacy of a particular drug.

“Less than 1 percent of all opportunities are being realized with respect to genetic testing,” said Felix Frueh, president and head of genomics initiatives at Medco. “There’s a long way until this new technology is going to see the translation.”

Indeed, while new biomarkers are identified everyday, and researchers are continuing to collect more and more information about genetic variants that confer some amount of disease risk or predict a specific response to a treatment, that information has yet to be widely implemented in the clinic. The AMA states on its website that physicians today can use more than 1,200 genetic tests for more than 1,000 different diseases to help diagnose and treat their patients, but only 13 percent of the 10,000 doctors who responded to the survey had ordered a genetic test for a patient in the preceding 6 months.

But while physicians by and large have been slow to adopt the practice of screening patients to search for genetic information of relevance to drug treatments, known as pharmacogenomics, neither research nor regulation has stalled, as evidenced by the FDA’s relabeling of dozens of approved drugs with biomarkers that affect their safety or efficacy in specific patient populations. “Pharmacogenomics is probably an area where personalized medicine is really able to deliver,” Frueh said, “and it is able to do so because those are tests that can be clearly associated with a particular therapy.” Read more…

Yale-Gilead Partnership to Investigate Genetic, Molecular Basis of Cancer

Captured by GenomeWeb

Gilead Sciences and the Yale School of Medicine today announced a collaboration to explore the genetic basis and molecular mechanisms of cancer in order to develop new cancer therapies.

The deal is initially for four years but may be extended for up to 10 years. Gilead will provide $40 million in initial funding to support research and basic science infrastructure development. Its contribution could reach $100 million if the collaboration is extended to the 10-year timeframe.

Under the terms of the deal, researchers from Gilead and Yale will work to identify new molecular targets in order to better understand cancer and to develop new treatments, including those to overcome drug resistance experienced by some patients with current therapies.

Gilead will have the first option to license Yale inventions resulting from the agreement. Read more…

Ohio State Genetic Counselors Elevating Role in Personalized Medicine

Captured by WCMH-TV/4 (NBC affiliate)

What if you could know what diseases were in your future by spitting into a tube?

A study in Columbus is doing just that – and it’s on the cutting edge of medical technology.

Researchers are mapping out an individual’s genetic predisposition to a number of diseases and health concerns, and it all starts with your spit.

Mother and daughter Janet Snapp and Carrie Buss are looking into their health history and future.

“You watch a lot of these crime shows and they just swab a DNA sample from your saliva. We thought they could … take it from our coffee cup, you know, and analyze our lipstick,” Snapp said.

“They come in, learn the information, we hand out the spit tube, everybody spits together. We get their sample, send it off to the lab. Eight weeks later, they get their result,” said Amy Sturm, a genetic counselor at The Ohio State University.

Sturm is overseeing the study in conjunction with the Coriell Institute for Medical Research, where they extract DNA from saliva.

“We all have genetic risk factors. It’s a part of human life. But this could maybe unlock, you know, what you have to look forward to in the future and most of these are completely modifiable conditions,” Sturm said. Click here to view news story. Read more…