Personalized

Medicine
By Yixuan Wang

The topic for this paper that I chose to research and write about is Personalized
Medicine. In this paper, I will be looking at the general definition of personalized medicine,
the impacts it has on the society, and how it is being used today especially in the cancer
research field.
What is personalized medicine? Personalized medicine is providing the right
patient with the right drug at the right dose at the right time1. This type of treatment rests
on the idea of being able to make the treatment of patients based on the patients
themselves. Therefore, each treatment method would be different in order to yield the best
and fastest results. This idea first started when doctors started to realize that there were
times when a specific treatment greatly benefited a patient with an illness, but when that
same treatment was used on another patient of the same illness, the results were not as
good. Therefore, this observation planted the thought that there were other factors such as
the environment, the lifestyle, and most importantly the patients genome that was
affecting how effective a medication or treatment was to the patient. And after the Human
Genome Project started, which sequenced the human genome and identified the genes it
contained, scientists had the foundation set for them. With this information came the drive
to use the genome to identify different genes that caused diseases and to use personalized
medicine to combat them.2
Personalized medicine, once the end result had been reached, would be greatly
beneficial to society. Because most of the medicine being produced today is geared for the
general public, often times the medication would be used for anyone with the described
illness. And because of that generality, often times a medication would be accompanied by
a long list of possible side effects, some being light like nausea and some being harsh, such
as internal bleeding. And with the generality of the medications being sold today, the
current method used by doctors to treat patients is the trial-and-error approach. When a
patient comes in, the doctor has a myriad of drugs that may help. However, it is difficult to
discern which to use, so the doctor can only pick one and test it out. If there seems to be
no effect or dangerous side effects occur, the doctor will switch to another medication.3
Ultimately, it is the patients themselves that are affected by any possible medication
failures. In fact, an estimated 2.2 million adverse drug reactions occur each year in the
United States, including more than 100,000 deaths.3 Some of these illnesses and their
corresponding percentages of ineffectiveness is shown in Figure 23.
So big are this problem and the possibility of a solution through personalized
medicine, earlier this year Obama declared his plan to issue a policy called the BRAIN
Initiative4. Also known as the Precision Medicine Initiative, this policy would give $215
million to a variety of different organizations for funding for personalized medicine
research. He hopes to dictate $130 million for the National Institutes of Health to create a
research group of a million volunteers who will analyze data; $70 million to the National
Cancer Institute for research to fight the disease; $10 million to the U.S. Food and Drug
Administration to develop databases needed to support aspects of the program; and $5
million to secure patient data-sharing across systems4. And with the passing of this policy
in the budget plan, the field of personalized medicine will expand even further than what is
has now affected not only scientists, doctors, and patients, but everyone in society.




















In personalized medicine there are a variety of different subfields and areas of
research. For example, scientists have tried to use proteomics. Others have attempted to
look at environmental factors on patient variability. Others focus on a specific area of
medicine or a specific disease. Others are attempting to ultimately develop a specific drug
to treat patients while another groups of scientists a focused on technology and machines
to help diagnose patients. In this paper, I will be focusing more on pharmacogenetics and
its relationship with cancer research.
Pharmacogenetics is an area of research that tests small variations within genes to
help identify differences in a persons ability to activate and deactivate drugs5. With the
knowledge of how the drug will be used, doctors can determine what drugs and how much
to give patients that will maximize the effectiveness of the drug and minimize the
dangerous side effects. Currently, most drugs are one-size-fits-all for the treatment of
cancer. In addition, in the cancer field, studies have shown that different tumors have
different mutations, even if the cancer started in the same organ and that a recurrent
cancer (a cancer that comes back after treatment) has different mutations than the original
cancer5. This finding makes it even more difficult for treatment yet makes personalized
medicine and pharmacogenetics even more appealing. If the specifics of how the body
interacts with a treatment is identified, cancer at all stages and types can be combated.
The benefits of pharmacogenetics are that there will be an improvement of patient
safety, a more powerful medicine that can shorten the time of hospitalization, and an
improvement in health care costs and efficiency once all the non-effective or harmful drugs
are not given to patients5-6. However, there are challenges. The major setback is that there
are so many types of cancers and so many genes that could cause these outcomes. Finding a
personalized drug for each profile will take years is not decades. In addition, there is
always the possibility that the cancerous cell will eventually become resistant to the
treatment, thus warranting it useless. And finally, while drugs that are tailored to the needs

of the patient can be very effective, sometimes more is needed to combat cancer. If cancer
were to be defeated, all areas need to be improved7.
How the drugs that treat cancer work is that when injected or taken, the drugs are
not in the active form and are called prodrugs5. Enzymes in the body are what activate
these drugs. However, the problem is that each person is born with a unique amount of
these enzymes. Therefore, in one person with a lot of the specified enzymes the drug will
quickly take into effect. However, in another person with much less enzymes, the effect of
the drug will take much longer. The same thing goes with deactivation of the drug. This
variation in deactivation time can lead to normal or healthy tissues in the body being
negatively affected5.
As of right now, there are two areas that are being researched in pharmacogenetics:
genes encoding either metabolic enzymes that can alter a drugs activity or defective
structural proteins that result in increased susceptibility to disease6.
Before going deeper in how pharmacogenetics is related to cancer research, it is
important to understand the basics of what cancer is and how it works. Cancer occurs
when normal cells start to divide without regulation. It is the genes that cause this change
in the normal cells. Due to a mutation of some kind, either a mutation that prevents the cell
from stopping and killing an abnormal cell or a mutation that increases the amount of
division of the cell, a large ball of cells called a tumor can develop. There are two main
types of tumors benign and malignant. Benign tumors develop but do not spread. Usually
this tumor is considered safe and can usually be removed by surgery. However, the
dangerous type of tumor is the malignant type. This type of tumor is cancerous and will
grow and spread, infecting other parts of the body. In addition, it can often times grow back
despite surgery8.
So how do those researching pharmacogenetics attempt to solve this issue? Because
cancer is caused by a mutation in the genome, scientists are using DNA sequencing and
analysis of patient tumors to find new genetic alterations associated with specific cancers9.
The scientists first locate the different genes that cause the growth of certain tumors and
then test different drugs to determine which one is the most specific and effective. Once the
treatment or medication is determined, those with the specific mutated gene will be given
the treatment.
Overall, there have been many organizations and studies going on that all aim to add
information to the goal of using personalized medicine. One of the biggest projects in the
cancer research field is called The Cancer Genome Atlas Project (TCGA). Started in 2006 by
the NCI and the NHGRI, the goal of this project was to create a map of various cancer
genomes in order to better understand what turns a normal cell into a cancer cell and what
makes one cancer different from another5. Here, tissue samples from patients with cancer
is collected by biopsy and is compared with tissue samples from patients without cancer.
By mapping the genome of the two different types of tissues, scientists can see which genes
are different. Of course not all different genes cause cancer. Instead, the scientists look at
any familiar patterns or trends from patients with the same cancer to identify the drivers
(gene mutations that allows for the cell to grow into a tumor). Ultimately, once completed,
this project will produce comprehensive characterization of cancer genomes from 24 of
the most common as well as 9 of the most rare tumor types10.
Another interesting study is by Dr. Getz and his team. They used nearly 5000 tumor
and matching normal-tissue samples spanning 21types of cancer and used an algorithm

called MutSig to identify passenger mutations from driver mutations11. The result was the
identification of nearly all the cancer genes of the 21 types of tumors and 33 new ones11.
Not only have there been results from these two studies. In fact, from 2010 to 2012
the FDA had approved four cancer drugs that targeted specific genetic characteristics3. The
drug imatinib (Gleevec) was used to inhibit an altered enzyme produced by a fused
version of two genes found in chromic myelogenous leukemia9. The drug cetuximab
(Erbitux) has been made to combat a mutated gene called KRAS, which causes a tumor for
colon cancer9. And for breast cancer women patients with the HER-2 positive profile, the
drug traxtuzumab (Herceptin) can be taken9. And this short list is but a few of the
personalized medication for cancer. There are more to be made for both the cancer field
and other diseases and gene mutations.
In conclusion, personalized medicine will be an essential part of medicine in the
future. Not only does it make it easier for doctors to discern which drugs to prescribe to
patients, it can also help combat some of the long-term medical problems such as cancer.
The future direction of this study on personalized medicine is the integration of specialized
drugs and technology into clinical practice for all diseases and for all patients. While there
will be setbacks in the future, with the support of the government and the enthusiasm of
scientists and doctors, I believe that personalized medicine will one day become a normal
part in the practice of medicine.

Resources:

"FDAs Unique Role and Responsibilities in Personalized Medicine." Personalized Medicine.
FDA, 30 Jan. 2015. Web. 03 May 2015.

Ginsburg, Geoffrey S. "Genomic and Personalized Medicine Volumes I & II." Science Direct.
Ed. Huntington F. Willard. Elsevier B.V., 2013. Web. 3 May 2015.

Administration, Food And Drug. Paving the Way for Personalized Medicine (n.d.): n. pag.
Paving the Way for Personalized Medicine. FDA, Oct. 2013. Web. 3 May 2015.

Richinick, Michele. "Obama Seeks $215 Million for Personalized Medicine." Msnbc.com.
NBC News Digital, 30 Jan. 2015. Web. 03 May 2015.

"What Is Personalized Cancer Medicine?" Cancer.Net. American Society of Clinical
Oncology, 23 May 2012. Web. 03 May 2015.

"Pharmacogenomics." Pharmacogenomics. American Medical Association, 2015. Web. 03
May 2015.

"Targeted Treatments." Cancer.Net. American Society of Clinical Oncology, 19 Dec. 2013.
Web. 03 May 2015.

"What Is the Difference between a Benign and Malignant Tumour? Pancreatic Cancer
Action." Pancreatic Cancer Action ICal. Pancreatic Cancer Action, 2015. Web. 03 May
2015.


"Impact on Precision Medicine." The Cancer Genome Atlas. U.S. Department of Health and
Human Services, n.d. Web. 03 May 2015.

Tarnuzzer, Roy W. "Steps Towards Precision Medicine: Utilizing FFPE Specimens." The
Cancer Genome Atlas. U.S. Department of Health and Human Services, 3 July 2014.
Web. 03 May 2015.

Mendoza, Jean H. "Filling in the Gaps in the Catalog of Cancer Genes." The Cancer Genome
Atlas. U.S. Department of Health and Human Services, 12 June 2014. Web. 03 May
2015.