| | Promise of personalised medicine | | AN Nagappa & Allani Pavan Kumar, Wednesday, January 5, 2011, 08:00 Hrs [IST] |
| | Modern medications save millions of lives a year. Yet any one medication
might not work for you, even if it works for other people. Or it might
cause severe side effects for you but not for someone else. Why do
medications act differently on different people? Sometimes despite all
of that, neither you nor your doctor knows how you'll actually react to
the medication. You may experience terrible side effects - or none at
all. Would your teenaged son buy the same clothes as his grandfather?
Probably would not. Would you still stick to your age old car while you
got a chance to buy a new model Mercedes. Of course not. But when we are
sick, we are likely to receive just about the same treatment and drug
choices. And so will everyone else. Personalised medicine is a medical
model emphasizing the systematic use of information about an individual
patient to select or optimize that patient's preventative and
therapeutic care. Personalised medicine can broadly be defined as
products and services that leverage the science of genomics and
proteomics (directly or indirectly) and capitalize on the trends toward
wellness and consumerism to enable tailored approaches to prevention and
care. Personalised medicine is moving us close to more precise,
predictable and powerful medicine - customised for the individual
patient. It is obvious that the concept "one medicine for all patients
with same disease" does not hold and more individual approach is needed.
Personalised
medicine involves the systematic use of information about each
individual to select or optimize the patient's preventative and
therapeutic care. It is the use of molecular analysis to better manage a
patient's disease or predisposition toward a disease.
People
vary from each another in many ways - the way they eat, the types and
amount of stress they experience, exposure to environmental factors, and
of course their genetic makeup. Many of these variations found in our
genes could influence our risk of developing a certain disease and the
degree to which it progress. Variations in several genes can influence
how well a patient might respond to a particular drug. Humans are unique
individuals. With the exception of identical twins, our genomes are
unique as well. Though all of us are genetically very similar, there are
small differences in our DNA that are unique and which makes us unique
in terms of health, disease and our response to certain treatments.
Personalised
medicine hopes to use these variations to develop new safe and
effective treatments for genetically defined subgroups of patients. The
natural variations found in our genes play a role in our risk of getting
certain diseases. The combination of these variations across several
genes along with numerous external factors such as environment, diet and
exercise affect each individual's risk. Natural genetic variations also
are part of the reason that the same drug works well in one individual
and not in another. Variations in DNA can lead to differences in how
drugs are absorbed, metabolised and used by the body. Understanding
these genetic variations and their interactions with environmental
factors will help researchers produce better diagnostics and will help
physicians better select treatments and dosing based on individual need.
The
past few years have witnessed a revolution in the understanding of
health and disease, brought on in large part by the sequencing of human
genome and the creation of map of human genetic variation. Personalised
medicine is the translation of this knowledge to patient care by using
genetic and genomic information in diagnosis, prognosis and treatment.
The goal of personalised medicine is to provide the right diagnosis and
treatment to right patient at right time at right cost. Major
investments in basic science have created an opportunity for significant
progress in clinical medicine. Researchers have discovered hundreds of
genes that harbour variations contributing to human illness, identified
genetic variability in patients' responses to dozens of treatments and
began to target the molecular causes of some diseases. In addition
scientists are developing and using diagnostic tests based on genetics
or other molecular mechanism to better predict patients' responses to
targeted therapy.
Variation from traditional medicine
In
general, traditional medicine, consider vastly used allopathic medicine
aims to treat the disease rather than the patient. For example to treat
a patient suffering from diabetes it considers external symptoms of the
patient, measure blood glucose level and prescribe the drug of choice
as per the symptoms, and we don't know "how effective the therapy would
be and how does the patient respond to it?" But in case of personalised
medicine it not only considers the above criteria while diagnosis and
treatment but also considers patient's proteinaceous, genetic and
metabolic profile for the understanding of impact of genetics in disease
and assess patient's risk factors for better therapeutic care.
Benefits of personalised medicine
The
drugs and treatments we devise are tested on broad populations and are
prescribed using statistical averages. For example, on an average, any
given prescription drug now on the market only works for half of those
who take it. Among cancer patients, the rate of ineffectiveness jumps to
75%. Anti-depressant drugs are effective in only 62% of those who take
them. Personalised medicine is beginning to transform the practice of
medicine. It is allowing health care providers to:
Shift the emphasis in medicine from reaction to prevention
Predict susceptibility to disease, improve detection, pre-empt disease progression
Customize disease - prevention strategies
Prescribe more effective drugs and avoid prescribing drugs with predictable side effects
Reduce the time, cost and failure of pharmaceutical clinical trials
Eliminate trial-and-error inefficiencies that inflate health care costs and undermine patient care
Current applications
Though
described as the phenomenon of the future, personalised medicine is
already having an impact on patient treatments. Molecular testing is
being used to identify those affected by breast cancer and colon cancer
are likely to benefit from new treatments and newly diagnosed patients
with early stage invasive breast cancer and now be tested for the likely
hood of recurrence. In another example, a genetic test for patients
with an inherited cardiac condition can help their physicians determine
which course of hypertension treatment to prescribe in order to minimize
serious side effects.
Blood clots
Before availability
of genome-based molecular screening, the dosing of warfarin, which
prescribed 21 million times a year, was a dangerous game in which too
little of the drug could trigger more clots and too much could lead to
excessive bleeding. Science 2007, the US FDA has recommended genotyping
for all patients being assessed for therapy involving warfarin.
Genotyping allows prescription of drug therapy regimens only to
individuals expected to benefit from that specific drug at that specific
dosage.
Colorectal cancer
Metastatic colorectal cancer
kills more lives than are lost to breast cancer and AIDS combined.
Among the drugs most frequently used is "cetuximab". For colon cancer
patients, the biomarker that predicts how a tumor will respond to
certain drugs is a protein encoded by the KRAS gene, which can be now be
determined through a simple test. Because cetuximab is effective only
in colon cancer patients with normal KRAS gene, treatment with drug can
be withheld from 40 per cent of patients for whom it would prove
ineffective. Alternative therapies can be pursued immediately instead.
Breast cancer
Just
as molecular diagnostic testing of tumors determines which colon cancer
patients are most likely to benefit from drug therapy using cetuximab,
women with breast tumors can be screened to determine which receptors,
if any, their tumor cells contain.
For example, the cells of the
highly aggressive "triple-negative" breast cancer have no oestrogen,
progesterone, or human epidermal growth factor receptors, which are
essential to the efficacy of current anti-breast cancer therapies. The
application of personalised medicine eliminates both the considerable
expense and precious time of trail-and-error treatments and helps
clinicians to determine quickly which breast cancer therapies are most
likely to succeed.
While still in the early stages, personalized
medicine is steadily emerging as the new healthcare business
opportunity. In the US, the total market for personalized medicine
currently is estimated at $232 billion and is projected to grow 11%
annually, nearly doubling in size by 2015, to a total of $452 billion,
according to PricewaterhouseCoopers' estimates. The core segment of the
market - consisting primarily of diagnostic tests and targeted therapies
- is estimated at $24 billion, and is expected to grow by 10% annually
to $42 billion by 2015.
(The authors are with Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576104) |
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