Since initial sequencing and analysis of the human genome was
accomplished [1,2], a huge effort has been put into medical research
focused on associating genomic variations with individual phenotypes.
Personalized medicine is often defined as “the right treatment for the
right person at the right time.” While the market for diagnostic tests
and therapies that leverage this new science is growing, the biggest
opportunities exist outside of the traditional healthcare sector. The
Personalized Medicine market is projected to grow by 11.56 percent
annually and is expected to reach US $148.4 billion by 2015. While
personalized medicine is already being considered in drug development
strategies, it is still at an early stage with respect to clinical applications
that support patient-specific therapy.
Genetic polymorphisms and mutations in drug metabolizing
enzymes, transporters, receptors, and other drug targets (e.g., toxicity
targets) are linked to inter-individual differences in the efficacy and
toxicity of medications as well as risk of genetic diseases. The interindividual
variation in the rate of drug metabolism has been known for
many years. Pharmacogenomics dealing with heredity and response
to drugs is part of science that attempts to explain variability of drug
responses and to search for the genetic basis of such variations or
differences. Validation of clinically important genetic polymorphisms
and development of new technologies to rapidly detect clinically
important variants are critical issues for advancing personalized
medicine.
The highest impact on personalized medicine is often seen for
drugs with a narrow therapeutic index, with important examples
emerging from treatment with antidepressants, oral anticoagulants,
and chemotherapeutics, which are metabolized by CYP2D6/CYP2C9,
VKORC1, and TPMT, respectively. To apply the ever increasing
amounts of pharmacogenomics knowledge to clinical practice,
specific dosage recommendations based on genotypes will have to
be developed to guide the clinician; and these recommendations will
have to be evaluated by the use of prospective clinical studies. Such
efforts will lead to the development of personalized medicines, which
would be expected to exhibit higher efficacy with fewer adverse drug
reactions, thereby improving the therapeutic index for drugs whose
pharmacokinetics, pharmacodynamics, and safety are influenced
by pharmacogenetics. In fact, to improve drug safety, the FDA has
started to update labels of previously approved drugs as new clinical
and genetic evidence accrues [3]. Increases in efficacy and safety by the
individualization of medical treatment may have benefits in financial
terms, if information is presented to show that personalized medicine
will be cost-effective in healthcare systems.
While the scientific community has largely accepted the utility of
sequencing for research purposes [4,5], the use of the next-generation
sequencing (NGS) technology in a clinical setting has yet to be fully
addressed or accepted by the medical community. To effectively
advance personalized medicine, it is necessary to be able to rapidly
and conveniently test for patients’ genetic polymorphisms and/or
mutations. Recent years, new technologies are evolving to transform
diagnostic devices for rapid testing at the Point-of-Care (POC).
Portable devices are being engineered for use in a range of settings to
perform robust assays for the diagnosis of disease that will improve
patient management, and result in greater convenience and speed to
answer. Current isothermal nucleic acid amplification methods include
nucleic acid sequence-based amplification (NASBA) [6], transcriptionmediated
amplification (TMA) [7], signal-mediated amplification
of RNA technology (SMART) [8], helicase-dependent amplification
(HDA) [9,10], recombinase polymerase amplification (RPA) [11,12],
loop-mediated amplification (LAMP) [13,14], cross-priming
amplification (CPA) [15], smart amplification (SmartAmp) [16,17],
rolling circle amplification (RCA) [18], and ramification amplification
(RAM) [19]. Among them, SmartAmp has the capability of clinical
genotyping [17].
The next important step is to incorporate pharmacogenomics data
into routine clinical practice. A key requirement for the advancing
personalized medicine resides in the ability of rapidly and conveniently
testing patients’ genetic polymorphisms and/or mutations. The POC
diagnostics is a growing field that is gradually becoming more userfriendly
with the introduction of portable devices and quicker nucleic
acid detection. Successful POC diagnostics require 4 major elements,
such as rapid reaction, low cost, low energy consumption, and simple
analysis (with minimal technical training and inclusion of controls but
no off-instrument processing or reagent preparation). Development
of personalized medicine including POC diagnostics may require
integration of various segments of biotechnology, clinical medicine,
and pharmacology.
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