As the 21st century approaches its teenage years, so too does molecular medicine. Discovery of the structure of DNA more than 50 years ago launched the field of molecular biology. During the last decade, we have seen the first translation of some fundamental discoveries in this field into medical tools. Clearly, however, we are early in their development for routine clinical use.
The biggest question for the next decade is whether molecular medicine can survive its teenage years, moving from first discoveries to mature approaches enabling inexpensive, practical, and reliable clinical tools.
Healthcare spending now represents more than 16 percent of the United States gross domestic product and is growing rapidly. The traditional approach to treating disease is reactive: we typically wait until someone is sick before treatment. As many health care professionals realize, a radical departure from this approach is required to contain healthcare costs. The key is to shift from diagnosing patients when they already have symptoms to detecting disease much earlier, before symptoms appear. This is the potential that molecular medicine brings to personalized healthcare delivery. Personalized healthcare will be predictive and preventive, probing an individual’s unique biology to assess disease probability and then designing appropriate treatments, even before symptoms. Many healthcare professionals believe this transformation will shift how the nation’s healthcare dollar will be used over the next decade, dramatically reducing the amount spent on today’s reactive treatments, while increasing the amount spent on prediction and diagnosis to almost a third of all expenditures.
Most work to date in molecular diagnostics has focused on identifying disease biomarkers in the blood or other easily obtainable bodily fluids. Developing comprehensive yet personalized assays for diverse populations, however, is highly complex and expensive.
Another approach is to focus on molecular screening in which tests based on blood-borne biomarkers are tuned for high sensitivity (which means you never let a patient with the disease go undetected) but relatively low specificity (which means you may predict a number of healthy people have the disease – i.e., significant false positives). Typical diagnostic tests today must balance between sensitivity and specificity because of the high cost usually associated with false positives.
Under the new model, depicted in the figure, molecular screening first identifies a high risk individual. Screening results are augmented by highly specific molecular imaging tests to confirm disease onset, characterize the disease, and determine location.
Finally, molecular therapies can be delivered noninvasively, and molecular imaging can be used to both guide procedures and assess treatment efficacy. This integrated approach, including several feedback loops specific to the patient, will be more affordable and reliable, as highly specific imaging can greatly reduce false positives that create unnecessary expenses and anxiety today. Overall, it will help translate molecular medicine into a robust personalized tool.
This model of molecularly-enabled, personalized medicine will become a reality in the next decade only if the following five questions can be successfully answered:
Will molecular screening technologies based on genomics and proteomics be able to detect the early onset of complex diseases such as diabetes and cancer?
Molecular screening has made tremendous progress in the last decade. This progress, however, has produced new challenges. For example, the volume of data required to screen for an array of complex diseases touching many molecular pathways in the body is enormous. Complementary genomic, biomolecular, and IT tools are required to translate the promise of molecular screening into a robust gatekeeper for all of molecular medicine.
Can molecular imaging provide a cost-effective tool to confirm disease onset, characterize the disease, and determine its location?
In the last decade, molecular nanosystems have been developed primarily for nuclear medicine (e.g., positron emission tomography scanning). More recently, optical, magnetic resonance imaging, and ultrasound probes have been synthesized, but they generally lack either the sensitivity or targeting specificity required for molecular diagnostics. Also, the cost of current molecular imaging procedures is prohibitive for routine clinical use. A cost-effective molecular imaging procedure with both high sensitivity and high targeting specificity must be developed in the next decade to complement molecular screening tools.
Can robust molecular delivery systems be developed to enable targeted drug and biologic therapies at the individual cell level?
At the start of this century, there was great hope that targeting systems could be developed to deliver drugs and modern biologic therapies (e.g., siRNA) with high specificity, sparing the side effects commonly associated with chemotherapies. Although great progress has been made during the last decade, there still is not a robust family of vehicles for targeted delivery, especially at the intracellular level. One of the primary goals of the next decade is to enable intracellular therapeutics (i.e., therapy directed to intracellular targets within a single diseased cell) through engineered delivery systems of great specificity.
Can molecular therapies be monitored non-invasively and cost-effectively to provide a tight feedback loop guiding personalized therapies?
Molecular therapies must be monitored effectively to maximize therapeutic efficiency while simultaneously minimizing side effects. A key goal for the next decade is to develop multi-functional molecular nanosystems that can simultaneously provide the delivery mechanism for intracellular therapies while at the same time serve as an imaging probe able to monitor the effectiveness of these therapies.
Can molecular nanosystems be developed for targeted diagnostics and therapeutics with no long-term toxicity?
Many molecular nanosystems have been developed in the last decade with little or no short-term toxicity. However, no molecular nanosystem for targeted diagnostics and therapeutics has yet been developed that eliminates all concerns about potential long-term toxicity. Eliminating long-term toxicity must become as much as of a design goal for molecular nanosystems in the next decade as sensitivity and specificity were in the last decade.
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