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General interest items edited by Janice Flahiff

Precision medicine is ‘personalized, problematic, and promising’

Precision medicine is ‘personalized, problematic, and promising’.
F
rom the  10 July 2015 University of Pennsylvania news release

Since President Barack Obama’s State of the Union Address in January 2015, the nation has been talking about a revolution in patient care, known by many as precision medicine.

Of course, the country is used to hearing the president talk about health care, especially the Affordable Care Act. But when the White House starts launching $215 million initiatives to accelerate research—in this case, the Precision Medicine Initiative, according to a White House Press release—you can be sure it’s not just a passing fad.

First, what is precision medicine?

Precision medicine is about tailoring treatments to the patient’s genome and body function. The promise is that this detailed personal health data can determine what’s most effective for each individual, which can lead to better outcomes.

Most of precision medicine’s application currently focuses on cancer. Launched in 2013, Penn Medicine’s Center for Personalized Diagnostics (CPD) helps oncologists determine the best treatment for their cancer patients by looking at the cancer’s genome.

Here’s how precision medicine is being practiced at Penn:

  1. A patient is diagnosed with cancer.
  2. If the cancer involves a solid tumor—like breast, lung, or colon cancer—the tumor is surgically removed during a biopsy, and a chunk of the tissue is sent to Penn Medicine’s CPD. If the cancer involves blood or bone marrow—like leukemia—a sample of the blood or bone marrow is sent.
  3. The CPD sequences a panel of genes that are known to be involved in cancer. This test examines DNA within the tumor, blood or bone marrow sample. The goal is to find DNA mutations that are driving the cancer.
  4. A report on the mutations found is sent to the patient’s oncologist.
  5. The oncologist determines if there are therapies or treatments available that work better than others—or not at all—on the patient’s particular type of cancer.

“We’re using precision medicine to give patients the right drugs, guided by the DNA sequence information from their cancer, so we’re not exposing them to potentially toxic effects,” explains David Roth, MD, PhD, director of the CPD. “This individualized therapy is better than treatment based on the ‘average patient.’”

Precision Medicine is being researched, translated and applied across Penn Medicine. Here,
experts from the Center for Personalized Diagnostics share four predictions on how precision medicine will change how cancer is treated in future generations.

1. Cancer will be diagnosed earlier.

Jennifer Morrissette, PhD, clinical director of the CPD:

“There are different stages of tumors. The earlier you catch the tumor, the more likely you are to survive it. My theory is that this century will be the century of diagnostics. We will be diagnosing people’s cancers earlier and earlier.

“That way, we are not dealing with advanced metastatic tumors that have acquired so many different changes that they’re hard to treat. We’ll be capturing tumors very early, in stage one; have a definitive surgery; follow the patient for a certain number of years to make sure that the cancer hasn’t spread; and then they’ll be cured.

“Some people put off seeing a physician because they don’t want chemo, but the longer they put it off, the more likely they are going to have metastatic disease.”

2. Cancer treatment will be based on each person’s health profile.

David Roth, MD, PhD, director of the CPD:

“[In the past,] doctors had been treating [the average patient] based upon results from a large study.

“The revolution in precision medicine is that now we have better tools to understand what’s going on with you as an individual. Instead of saying, ‘Okay, you have this particular cancer, and you have a 30 percent chance. So, go ahead and get this toxic therapy,’ we can be much more specific.

“If we were able to tell you that you have a five percent chance of responding to a chemotherapy based on the makeup of your tumor, would you still do it?”

3. Gene paneling will be used for diagnosis, not just treatment.

David Lieberman, MS, CGC (certified genetic counselor):

“We tend to see certain genes mutated in certain cancers. For example, there is a certain set of
genes [that are] typically mutated in lung cancer or another set in lymphoma.

“It is not always clear using historical methods what type of cancer a patient has. This makes treatment decisions challenging. Sequencing the tumor’s DNA on a panel of known cancer-related genes may help clarify the cancer’s origin and, in this way, assist the clinician in determining treatment or prognosis.”

$215 million: The amount the White House will invest in the Precision Medicine Initiative in 2016
Source: WhiteHouse.gov

4. More cancer patients will have a treatment team, rather than just an       oncologist.

Jennifer Morrissette PhD, clinical director of the CPD:

“It’s not going to be one physician making all the decisions. Cancer treatment has gotten much more complex. Because of the availability of multi-gene testing, you need a group of people with different types of expertise to make the best decision for a patient.

“In addition to the team directing care for the appropriate approach—whether it’s surgery, radiation, chemotherapy, pain management—now there is also the genetic component.

“[The team’s] able to sit in a room with people from the lab who can talk about what the result means, have the oncologist tell them about the patient and then get the clinical geneticist’s notion that there may be an inherited predisposition. Then, they walk out with a consolidated treatment plan for that patient.”

The future of medicine

For more than 250 years, advancements like “precision medicine” have been the hallmark of Penn Medicine. As the first school of medicine in the United States, it has been and continues to be a place where the future of medicine and the future leaders in medicine are being developed.

July 19, 2015 Posted by | health care, Medical and Health Research News | , , , , , , | Leave a comment

[Repost] Database of Disease Genes Shows Potential Drug Therapies

From the 10 October 2013 article at newswise 

            [From the  article abstract – The Drug-Gene Interaction database (DGIdb) mines existing resources that generate hypotheses about how mutated genes might be targeted therapeutically or prioritized for drug development. It provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially ‘druggable’ genes. DGIdb can be accessed at http://dgidb.org/.]

Newswise — Researchers at Washington University School of Medicine in St. Louis have created a massive online database that matches thousands of genes linked to cancer and other diseases with drugs that target those genes. Some of the drugs are approved by the U.S. Food and Drug Administration, while others are in clinical trials or just entering the drug development pipeline.

The database was developed by identical twin brothers, Obi Griffith, PhD, and Malachi Griffith, PhD, whose interest in pairing drugs with genes is as much personal as it is scientific. Their mother died of breast cancer 17 years ago, just weeks before their high school graduation.

“We wanted to create a comprehensive database that is user-friendly, something along the lines of a Google search engine for disease genes,” explained Malachi Griffith, a research instructor in genetics. “As we move toward personalized medicine, there’s a lot of interest in knowing whether drugs can target mutated genes in particular patients or in certain diseases, like breast or lung cancer. But there hasn’t been an easy way to find that information.”

Details of the Drug Gene Interaction database are reported online Oct. 13 in Nature Methods. The database is weighted heavily toward cancer genes but also includes genes involved in Alzheimer’s disease, heart disease, diabetes and many other illnesses. The Griffiths created the database with a team of scientists at The Genome Institute at Washington University in St. Louis.

The database is easy to search and geared toward researchers and physician-scientists who want to know whether errors in disease genes – identified through genome sequencing or other methods – potentially could be targeted with existing drug therapies. Additional genes included in the database could be the focus of future drug development efforts because they belong to classes of genes that are thought to make promising drug targets.

“Developing the database was a labor of love for the Griffiths,” said senior author Richard K. Wilson, PhD, director of The Genome Institute. “There’s an amazing depth to this resource, which will be invaluable to researchers working to design better treatment options for patients.”

Wilson and his colleagues caution that the database is intended for research purposes and that it does not recommend treatments. The primary purpose of the database is to further clinical research aimed at treating diseases more effectively.

“This database gets us one step closer to that goal,” Malachi Griffith said. “It’s a really rich resource, and we’re excited to make it available to the scientific community.”

The database, which took several years to develop, is publicly available and free to use. It includes more than 14,000 drug-gene interactions involving 2,600 genes and 6,300 drugs that target those genes. Another 6,700 genes are in the database because they potentially could be targeted with future drugs.

Before now, researchers wanting to find out whether disease genes could be targeted with drugs had to search piecemeal through scientific literature, clinical trials databases or other sources of information, some of which were not publicly available or easily searchable. Further, many of the existing databases have different ways of identifying genes and drugs, a “language” barrier that can turn a definitive search into an exhaustive exercise.

The Griffith brothers are experts in bioinformatics, a field of science that integrates biology and computing and involves analyzing large amounts of data. The brothers got the idea for the drug-gene interaction database after they repeatedly were asked whether lists of genes identified through cancer genome sequencing could be targeted with existing drugs.

“It shouldn’t take a computer wizard to answer that question,” said Obi Griffith, research assistant professor of medicine. “But in reality, we often had to write special software to find out. Now, researchers can quickly and easily search for themselves.”

The new database brings together information from 15 publicly available databases in the United States, Canada, Europe and Asia. Users can enter the name of a single gene or lists of many genes to retrieve drugs targeting those genes. The search provides the names of drugs targeted to each gene and details whether the drug is an inhibitor, antibody, vaccine or another type. The search results also indicate the source of the information so users can dig deeper, if they choose.

The research is supported by a grant (U54 HG003079) from the National Human Genome Research Institute at the National Institutes of Health (NIH).

Griffith M, Griffith OL, Coffman AC, Weible JV, McMichael JF, Spies NC, Koval J, Das I, Callaway MB, Eldred JM, Miller CA, Subramanian J, Govindan R, Kumar RD, Bose R, Ding L, Walker JR, Larson DE, Dooling DJ, Smith SM, Ley TJ, Mardis ER and Wilson RK. DGIdb – Mining the druggable genome. Nature Methods. Oct. 13, 2013.

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare​.

 

October 15, 2013 Posted by | Consumer Health, Medical and Health Research News | , , , , , | Leave a comment

   

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