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February 11 2018

Mini-Medical School 2018 #1-The Precision Medicine Initiative

Stephanie Taylor MiniMedical School

The Precision Medicine Initiative
Stephanie Taylor MD PhD
Mini-Medical School #1 2018

The Precision Medicine Initiative is a National US research program that is different than anything we have seen before.  The Initiative applies massive computing power to analyze complex genetic relationships, aggregate massive amounts of data and discover new approaches to healthcare.  Precision Medicine customizes the medical treatment to the person as well as the specific disease.  https://allofus.nih.gov/

Three specific applications are:

Pharmacogenomics (the right drug, the right dose)

Assessment of individual genetic cancer risk

Individual tumor profiling for chemotherapy

Pharmacogenomics:

Drugs are “digested” differently by everyone. It is not just a matter of breaking down the original compound. There are an infinite number of speeds, routes and byways for metabolic pathways to progress. Fortunately, some of those pathways are well described and have a clear genetic basis.

A cheek swab will deliver enough DNA for analysis of the essential enzymes, and an individualized highway can be constructed. The formal name for one of these metabolic families is Cytochrome P450 isoenzymes. Some are fast, some are slow and some go to odd places. Any of these variations can result in too much, too little or abnormal byproducts of a drug causing side effects and a lack of therapeutic effect. These individualized pathways are specifically measured by pharmacogenomics testing.  When the report is resulted, there will be a list of preferred drugs, those that need modification and others that should be completely avoided. Because this is genetic, the results last a lifetime.

Right now, this testing is used only in special circumstances. Preliminary data show a dramatic decrease in office and ER visits with correct pharmacogenomics testing. Very soon, no one will be prescribed a drug that they are not profiled to safely consume.

Genetic Cancer Risk Analysis:

There are many reasons to pursue genetic cancer risk testing and the situations are as varied as the individuals tested. Evaluation starts with the family history of cancer. If there is a clustering of cancer in the family, especially early onset cancers, then genetic testing is recommended. If a person is identified as carrying the gene, then increased screening and early diagnosis and treatment can be lifesaving.  Knowing the genetic risk also allows screening of other family members, which can be additionally life-saving.

Most people are familiar with BRCA testing for hereditary breast and ovarian cancer.  This testing was pioneered by Myriad Genetics. There are now many more identified genes that increase cancer risk and there are now several companies offering genetic testing and counseling services.  A cutting-edge local initiative is the Project DNA, a website and initiative, created by a local gastroenterologist, Dr. Dan Luba. This has a wealth of well-organized information. There are fifteen individual syndromes listed as well as educational videos and a smart family history calculator. This can be accessed at: http://theprojectdna.com/about/.

Tumor Profiling:

Not all cancer that occurs in a single organ, such as the breast, has the same behavior. Some are lazy and some are aggressive. This tendency can be tested genetically.  For example, HER2/neu is a protein that, when present in excess, affects breast cancer management. First, it changes prognosis, indicating a more aggressive tumor. Secondly, it allows a targeted therapy with Herceptin. Only HER2 expressing tumors are treated with drugs that specifically target HER2.  There are other HER2/neu targeting agents in clinical trials.
A tumor can also change its genetics over the course of therapy and a sophisticated change of chemotherapy may be lifesaving. Rapid genetic profiling of the current tumor genetics would allow immediate re-design of chemotherapy and is aggressively researched at many major universities.

Resources:  (endless)

Pharmacogenomics on the net: https://ghr.nlm.nih.gov/primer/genomicresearch/pharmacogenomics

Consider participating in the All of US Research Program of the Precision Medicine Initiative.
https://allofus.nih.gov/

You Tube video of Genetic Cancer: Search: “Introduction to Hereditary Cancer”.

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