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Revolutionizing and personalizing global health
April 2013
SHARING OPTIONS:
"Every generation needs a new revolution." Thomas
Jefferson's words are poignant and timely, as we sit on the cusp of an urgently
needed revolution to transform health on a personalized and global scale.
While we are buoyed by some extraordinary scientific and
medical breakthroughs in recent years, we are mindful that most common diseases
still cannot be effectively treated by existing therapies. Many cancers,
including breast, lung, colon and prostate, are incurable once they have
metastasized, while heart disease and stroke remain leading causes of
mortality. Based on the current trajectory, cancer and type 2 diabetes will
double by 2030, while Alzheimer's disease will triple by 2050. Consequently,
these and other rising non-communicable diseases are on track to wreak havoc
with most economies—and most families.
Environmental factors such as obesity and exposure to
pollutants are having a growing impact on our health, and left unchecked, will
outpace our ability to innovate cost effective solutions. These issues are
compounded with the impact of aging in most developed and many developing
countries. The largest global health study ever conducted (Lancet, Dec. 2012) showed that despite the fact that people are
living longer, they are doing so in poor health. For every year of longer life,
only 9.5 months are in good health, while the rest are in a diminished state,
and the numbers get progressively worse for people aged 50 and up.
This leaves us with the quadruple challenge of finding (1)
improved diagnosis/screening for early-stage detection and disease
predisposition; (2) personalized treatments that are safe and efficacious; (3)
the actual prevention of disease; and (4) affordable healthcare that does not
cripple global economies. While daunting, these goals are attainable, thanks to
the culmination of decades of research in genomics, epigenomics, proteomics and
other fields, yielding an unprecedented understanding of diseases as complex as
cancer, as well as mechanistic insight into environmental factors that impact
health. Broadly, the new transformative disciplines fall into six key
categories.
(1) Genomic analysis Next-generation sequencing (NGS) has transformed our
understanding of many diseases, especially cancer. Thanks to NGS, we understand
cancer to be a disparate collection of molecular diseases and should be treated
accordingly. NGS is increasingly being incorporated into clinical trials, and
may eventually be a routine stratification tool. Arguably the most impactful application of
NGS is in the clinic, in life-critical situations such as guiding treatment for
cancer patients and identifying rare disease-causing mutations in newborns.
Translating NGS from a research platform to a clinically useful tool has been
possible thanks to a dramatic shift in cost and efficiency, as well as key
ancillary technologies that enable efficient extraction of DNA from
diminishingly small tumor samples.
Coming swiftly upon the heels of NGS is the field of
epigenomics, which has grown exponentially over the past decade. Thanks to a
growing suite of analytical tools that can measure DNA methylation, histone
acetylation and microRNA expression in high throughput, we have the ability to
assess the molecular effect of specific environmental factors on the epigenome,
and link this to phenotype and disease causation. In the past year alone, we
have seen a wealth of evidence supporting an environmental link with diseases
such as cancer, types 1 and 2 diabetes, allergies, asthma and many others. We
are also learning about the direct molecular link between nutrition and energy
metabolism, and the effect on epigenetics and ultimately disease.
Using new innovative technologies to understand the direct
molecular influence of our environment on health is a significant step towards
figuring out how to stop—and ideally reverse—the imminent explosion of
non-communicable diseases.
(2) Biomarkers and
companion diagnostics
An important consequence of genomics and other 'omic
analyses has been the discovery and validation of a large, growing number of
clinically useful biomarkers and biosignatures. The impact of these on clinical
practice has been profound and swift, ranging from their inclusion in virtually
all clinical trials from the outset, through to their use in the clinic for
diagnosing patients and guiding treatment to ensure optimal safety and
efficacy. The greatest impact thus far has been in the field of cancer, where
the analysis of a patient's tumor biomarkers is increasingly becoming standard
of care.
As with genomics, the successful transition of biomarkers,
companion diagnostics and personalized medicine into mainstream clinical
practice is contingent on analytical tools that are accurate, robust,
efficient, scalable, cost-effective and that extract very large amounts of
information from exceedingly small clinical samples. Automation is key to
addressing the issues of efficiency, reproducibility, scale and cost, as
companies transition their diagnostic assays from small scale to commercial
launch. As samples become smaller and less invasive, the ability to multiplex,
measuring multiple biomarkers simultaneously, is critical for maximizing
information and enabling accurate diagnosis. Consequently, multiplexed
platforms are becoming increasingly important in personalized cancer medicine.
In the field of cancer, circulating tumor cells (CTCs)
represent a paradigm-shifting biomarker. CTCs are "liquid biopsies" based on a
blood draw, and thus are more amenable to routine screening. While it is well
established that the measurable presence of CTCs in blood is correlated with
poor prognosis for various solid tumor types, the clinical utility of this
approach has been limited by the poor sensitivity of the assay, providing
little clinically actionable information. In recent years, progress in
microfluidics and engineering has produced a new generation of CTC platforms
that are tenfold more sensitive than earlier versions, and allow isolation of
single cells for various omics analyses. One near-term benefit will be tests to
gauge a patient's response to a targeted therapy in days rather than weeks,
giving physicians vital time to adjust and find the optimum therapy.
(3) Imaging and
pathology
One important tenet of disease diagnosis and treatment
continues to be biological contextual and heterogeneity information, as these
provide clinically informative data that is lost with most omics technologies,
which typically use isolated homogenized samples. The continued strong growth
in histopathology highlights the importance of direct biomarker visualization
and contextual analysis. Multiplexing provides another important dimension,
maximizing clinically relevant information from each precious tumor sample.
Preclinical in-vivo
imaging continues to be one of the most critical enabling technologies in
translational medicine, allowing non-invasive longitudinal studies to track the
impact of therapeutic candidates in animals. The importance of these
technologies is underscored by the fact that many approved drugs were validated
preclinically using them, including Pfizer's Sutent and Lyrica, Roche's
Zelboraf and Novartis' Zometa.
Building on the success of in-vivo imaging, the same fluorescence-based imaging technologies
are being translated to human surgery, whereby they enable surgeons to
visualize precisely cancer tissues in real-time during surgery, and excise the
optimal amounts of tissue. Intraoperative imaging promises significant benefits
in cancer, reducing repeat surgeries as well as the risk of tumor spread from
non-excised cancerous tissue.
(4) Targeted small
molecules, therapeutics and vaccines
The availability of genomic information has transformed our
ability to design and optimize targeted small-molecule drugs and biologics that
can treat patients more safely and effectively. This is further enhanced by
layering in biomarkers and companion diagnostics, oftentimes enabling treatment
of diseases that were hitherto untreatable or that were not economically
viable, such as orphan diseases including many life-threatening cancers that
affect very small numbers of patients.
Underpinning the successful development of these novel
treatments has been the fusion of information from many disruptive tools that
span a broad range of platforms, from molecular and cellular assays, NGS,
high-throughput biomarker analysis, preclinical imaging to "high-context"
multiplexed immunohistochemical tissue imaging. A critical feature common to
the most useful tools is their ability to seamlessly translate from bench to
clinic across the "in-vitro to in-vivo to human bridge"—the great
divide that separates clinical success and failure. This is especially true for
cancer research, where many promising in-vitro
and preclinical candidates have failed when tested in humans.
(5) Cellular systems
One of the greatest objectives in medicine is treating the
underlying cause, rather than just the symptoms. Regenerative medicine,
although slow to start, is now gaining traction, with a growing number of stem
cell therapies in late-stage clinical trials spanning a wide range of acute and
chronic diseases. While still in relative stealth mode, regenerative medicine
should not be underestimated, particularly for addressing the impact of
age-related disease and thereby bending the healthcare cost curve.
Cardiovascular disease and neurological disorders, which
increase exponentially with age, can potentially be addressed using stem cell
therapies, as evidenced by very encouraging clinical progress on multiple
fronts. As with small-molecule and biologic therapeutics, innovative
translational tools that span the in-vitro
to in-vivo to human continuum have
been critical for establishing the safety and efficacy of these potent cellular
treatments.
(6) Informatics
The aforementioned technologies and disciplines are
generating mind-boggling amounts of data at an accelerating pace. The final
critical piece that fuses all of these data and helps leverage the tremendous
power of this information is bioinformatics. As the complexity and volume of
data continue to rise, bioinformatics is emerging as one of the cornerstones of
personalized medicine, from enabling discovery and development of novel
treatments and diagnostics to facilitating collection, analysis and
interpretation of data that ultimately helps an individual patient.
The convergence of biological information with the
availability of a formidable collection of disruptive and innovative tools that
enable personalized medicine leads me to believe that we now have the means to
affordably improve health through better diagnosis, treatment and prevention. Moreover,
the scalability of these tools combined with the rapid dissemination of
information means that the benefits in improved health will likely have a
global impact.
E. Kevin Hrusovsky was
appointed president of life sciences and technology at PerkinElmer Inc. in
November 2011 following the company's acquisition of Caliper Inc., where
Hrusovsky had served as CEO since July 2003. Prior to that, he served as CEO of
Zymark Corp. He received a B.S. degree in mechanical engineering from Ohio
State University and an M.B.A. degree from Ohio University.
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