Reported by Mike Miller
May 16, 2003
BenchMarks talked with NCI Director Andrew C. von Eschenbach, M.D., about his recently
announced challenge goal of eliminating suffering and death due to cancer by 2015. The
following is a transcript of that discussion.
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Dr. von Eschenbach was asked...
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You have issued a 'challenge goal' to eliminate suffering and death due to cancer by
2015. Why this particular goal, and why now?
Dr. von Eschenbach: I believe we are at what I call a strategic inflection in biology, which means we're at a point
of unprecedented growth in three key areas related to cancer research: knowledge, technology, and
resources. The integration of growth in these three sectors provides an opportunity for exponential
progress. To achieve this progress, we must set a clear direction and focus our efforts into a cohesive
strategy.
The goal of eliminating suffering and death due to cancer provides this focus. It does not mean "curing"
cancer but, rather, it means that we will eliminate many cancers and control the others, so that people can
live with -- not die from -- cancer. We can do this by 2015, but we must reach for it. We owe it to cancer
patients around the world -- and their families -- to meet this challenge.
Why is this goal feasible?
Dr. von Eschenbach: This is feasible because the intersection of exponential growth in biomedical research and the
explosion of enabling technologies has resulted in a "new science" of oncology. This goal is also
feasible because the fruits of cancer research since the signing of the National Cancer Act of 1971
have taught us a tremendous amount about cancer and brought us to a turning point.
We are now in the era of molecular oncology. We have more cancer researchers and more financial
resources than ever before in the history of medical research. I believe we have an unprecedented opportunity
to align our resources, our enabling technologies and our knowledge of cancer to achieve this goal.
And cancer research is not progressing in a vacuum. It contributes to, and benefits from, progress in
all of the life sciences.
Why do you say our knowledge of cancer has expanded exponentially?
Dr. von Eschenbach: To understand the impact of exponential growth, consider the question: "If you won the lottery,
would you prefer to collect one million dollars up front or one penny on day one and then double
it every day for just one month?" My advice to you is to take the doubling of the penny for one month.
At the end of one week you only have 64 cents and at the end of 2 weeks only $82, but by day 27, you will
have over $600,000 and by day 30 over $5 million. If pennies were knowledge, this would be the kind of growth
we are witnessing in cancer research, and we are no longer in the first or second week of this process, so
we can expect to continue to witness rapid expansion in our knowledge.
One strong indicator of our growth in knowledge is the number of published research papers on cancer.
By the time of the signing of the National Cancer Act in 1971, there had been only about 130,000 research
papers on cancer published, but today there are almost 1.5 million papers available.
More important than numbers of publications, however, is the profound new understanding that they have provided
us with regard to the normal growth of multicellular organisms and what goes awry in the case of cancer. And our
knowledge of intracellular pathways has grown dramatically.
We no longer see the cell as a mysterious "black box," but rather as a robust entity bombarded daily at its
surface by hormonal and chemical signals, signals from neighboring cells, and nutrients. We also know that
to remain alive and normal, an organism must decode, filter, and respond properly to many molecular conversations,
and we continue to learn about normal cellular pathways.
Today we understand cancer as both a genetic disease and a cell signaling failure. Genes that control orderly
replication become damaged, allowing the cells to reproduce without restraint. A single cell's progress from normal,
to malignant, to metastatic, appears to involve a series of interactive processes, each controlled by a different gene
or set of genes. These altered genes produce defective protein signals, which are, in turn, mishandled by the cell.
This understanding of the biology of cancer is enabling us to design interventions to preempt the cancer's progression
to uncontrolled growth.
What are some examples of exponential growth in enabling technologies?
Dr. von Eschenbach: It is instructive to look back at the progress technology has enabled in the past few decades. Shortly
after Watson and Crick's discovery of DNA, the 1960s ushered in electron microscopy. Its 100-fold increased
magnification enabled researchers to see DNA inside the tiny viruses called phages that infect bacteria. By
the end of the decade, the enzyme polymerase, used by these phages to copy DNA (deoxyribonucleic acid), was known. Then, in the 1970s,
phages were combined with enzymes like polymerase and ligase to develop technology for replicating DNA in a
test tube. This, in turn, enabled development of systems to study the regulation of DNA replication.
Technology in the 1980s emerged from basic research's discovery of restriction enzymes and reverse
transcriptase. Biochemical systems were created that could slice, dice, insert, delete, and mass produce
sections of DNA. This recombinant DNA technology enabled phages and bacteria to become factories for the
mass production of gene fragments, as well as entire genes and their corresponding proteins, even when RNA
(ribonucleic acid) was the starting point.
With the discovery of PCR (polymerase chain reaction) and automated gene sequencing in the 1990s, progress
in gene-protein discovery accelerated with unprecedented speed. Gene hunts that used to take 10 years to
complete could now be completed in two to three years.
This century finds technology such as gene and protein microarrays, high-throughput assays, robotics,
high-resolution NMR (Nuclear Magnetic Resonance), functional imaging, artificial intelligence, supercomputing
and, more recently, nanotechnology and iRNAs (interference RNAs), all at the service of today's researchers.
So what are we doing with all these technologies? Such sophisticated technology is being applied to better
understand how genes and proteins interact in normal and cancerous cellular networks. These technologies, coupled
with new disciplines such as genomics and proteomics, are improving our ability to predict cancer risk and to detect
and diagnose cancer earlier. Artificial intelligence and supercomputing already have been harnessed successfully to
analyze proteomic patterns for signatures of early-stage ovarian cancer.
New technologies are also making a huge difference in new drug discovery. High-speed nuclear magnetic resonance
spectroscopy, combinatorial chemistry, and new probes for functional imaging are changing how molecular targets are
identified and validated, and even how new interventions are designed. And supercomputing enables bioinformatics to
link the work of researchers across disciplines, so that interdisciplinary teams of scientists can rapidly and
effectively share information, insights, and accrual onto clinical trials.
These enabling technologies are creating a classic 'chain reaction', not at all unlike what the world witnessed
when scientists first discovered the secrets of the atom. Scientific discovery is fueling further scientific
discovery at an ever increasing rate of progress. This explains the exponential trajectory of our progress.
How has the biomedical revolution changed our understanding of cancer?
Dr. von Eschenbach: We've been able to understand that cancer is a disease process. It has a beginning and a
number of further steps that it must achieve if it is to become a lethal threat to a person.
We're increasingly able to describe cancer initiation and progression in terms of interactive
pathways and processes that lead to a lethal phenotype. Cancer must stop responding to anti-growth
signals from its neighbors, supply its own growth signals, evade self-destruction even though it
carries genetic error, recruit its own blood supply, then finally spread and invade other tissues
and organs. Only then does it become lethal.
We are now dissecting cancer from a genetic, molecular, and cellular perspective. This is teaching us about
the collective processes required for cancer progression and metastasis to occur, which will help us preempt
the process by slowing, delaying, or stopping it. The bottom line is that we now know that cancer and its
progression are vulnerable.
What strategy will NCI employ to reach the 2015 goal and how will it work?
Dr. von Eschenbach: We'll focus our efforts and accelerate our progress with what I call the "seamless three-D approach" to
cancer research -- the three Ds being discovery, development, and delivery.
Discovery is the process of generating new information about fundamental cancer processes at the genetic,
molecular, cellular, person, and population levels. This research allows us to identify the mechanisms
responsible for the initiation and progression of cancer in the cell and in the patient.
Development is the process of creating and evaluating tools and interventions that are of value in detecting,
diagnosing, predicting, treating, and preventing cancer.
Delivery involves promoting and facilitating the application of cancer interventions to all people who need
them. NCI does this in a research context in which monitoring the application yields not only information on
effectiveness, but insights into the human biology of cancer and its interaction with the patient. This requires
the use of research, communication, education and training, and technical assistance.
The three Ds are major components of our portfolio at NCI, not a strategy per se. Rather, our overarching
strategy is to create a greater degree of seamlessness between these three components than has existed in the
past. This enhanced seamlessness will dramatically accelerate the pace by which the fruits of discovery are
harvested for the benefit of cancer patients and the public at large.
This strategy continues NCI's historical emphasis on investigator-initiated basic research as the engine that
drives the entire biomedical research enterprise. We are absolutely committed to that course. The "seamless
three-D" strategy also builds on this strength by speeding translation of investigator-initiated discovery into
the development of new interventions and by accelerating the rate at which proven interventions are put into
widespread clinical and public health practice.
Beyond reducing the lag time from bench to bedside, the strategy will also offer important dividends to the
basic research community. Investing in initiatives that create greater seamlessness between the three Ds will
yield new tools and new platforms for collaboration that will enable members of the basic research community to
test their ideas quickly and move worthy science forward faster and better then ever before.
Implementation of this strategy is a work in progress, and will undoubtedly be revised continuously until
the challenge goal has been accomplished. One example of the strategy, however, is our current effort to bridge
the gap that sometimes exists between development and delivery by forming an historic partnership with the FDA
(Food and Drug Administration) to accelerate drug and device approvals. This partnership is emblematic of our
new approach.
What other initiatives is NCI putting in place to meet this goal?
Dr. von Eschenbach: Along with several key ongoing initiatives, such as molecular imaging and proteomics, we are
developing new initiatives and priorities in seven key areas: molecular epidemiology; integrated
cancer biology; strategic development of cancer interventions, including the FDA partnership which
I previously mentioned; early detection, prevention and prediction; an integrated clinical trials
system; overcoming health disparities; and bioinformatics [see sidebar article].
We'll adapt and refine these as we go, but the basic strategy in all of these initiatives is for
NCI to use its resources to remove barriers that currently inhibit progress broadly across the
discovery-development-delivery continuum. Whether re-engineering the clinical trials system to safely
accelerate progress of new interventions through the pipeline, or using bioinformatics to link people and
data together, or partnering with the FDA, we have an opportunity to accelerate progress throughout the
field of cancer research by eliminating the bottlenecks. We think of this as creating an "enabling culture"
that will accelerate progress both within and between the discovery, development, and delivery components
of our portfolio.
What is bioinformatics, and why do you believe it holds promise?
Dr. von Eschenbach: Bioinformatics is a discipline that uses information technology to create tools needed to
collect, share, and analyze biomedical data. With the surge in the amount of biomedical data
that we are now collecting, the ability to share and analyze this data efficiently and effectively
is key to making rapid progress against cancer. For example, in a single experiment, an
investigator can produce thousands of pieces of data about genes or proteins expressed in a
particular tumor. These parts and pieces of research data are often disconnected databases that
are difficult for colleagues to access. Similarly, there is often a data disconnect between
clinical trials on the very same agent.
We're working to integrate diverse databases and tools, enabling data sharing across the broadest
research community possible, encouraging collaboration and multi-disciplinary research, and ultimately
speeding delivery of an end product to the public. Our bioinformatics initiative -- by enhancing data
sharing -- will go a long way toward creating that enabling culture I spoke of a moment ago.
What drugs are in the pipeline that might help accelerate the goal?
Dr. von Eschenbach: At the end of 2002, there were 100 new cancer drugs in the Phase III stage of clinical
trials testing. But given that only a handful of drugs receive FDA approval every year, it's
obvious we need to do what we can to improve the process. That's why we're working jointly
with the FDA on building a partnership in several areas of cancer research. The FDA-NCI
proteomics program already has developed a promising screening tool for ovarian cancer and
more recently has developed a technique to evaluate drug efficacy.
But let's be clear. There's not going to be one single intervention that cures all cancers.
Instead, we'll be looking for combinations of agents or therapies that work together to shut
down cancer at vulnerable points in the progression process.
What will be done to reduce the suffering of cancer patients?
Dr. von Eschenbach: Allow me to answer this question at two different levels. First, we've renewed our focus on
symptom management and palliative care. Our Community Clinical Oncology Program (CCOP) supports some
60 clinical trials investigating such symptoms as cognitive dysfunction, fatigue, hot flashes, pain,
and nausea and vomiting. But much remains to be done in the palliative care field. We need to develop
less debilitating treatments, and we're exploring more effective ways to support patients and their
families during treatment and in the post-treatment phase.
Second, and perhaps more importantly, by slowing the progression of cancer and turning it into a
manageable disease, the burden of cancer, and the suffering that it causes, will be reduced. When
we can prevent cancer from progressing to its later and more virulent stages, we likewise will prevent
much of the suffering that accompanies those later stages.
Could we completely eliminate cancer by 2015?
Dr. von Eschenbach: Given the complexity of the myriad diseases that we call cancer, it's unlikely that
we will progress that far, that fast. But the point I wish to make is that a cure isn't
necessary to eliminate the worst aspects of the cancer experience -- suffering and premature
death. I do believe that by 2015, we can both eliminate some cancers as well as bring other
cancers under control as chronic, manageable diseases, much like people today live with diabetes
and heart disease. And one day, we may even eliminate cancer, but not in the foreseeable future.
What is foreseeable is to expand our ability to preempt the suffering and death caused by cancer.
That's why we've issued this challenge goal -- to focus ourselves on reducing the burden of cancer.
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