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National Cancer Institute
Annual Progress Report 2009

by John E. Niederhuber, MD, Director, National Cancer Institute

Author of Article photo

Cancer survivors face a special challenge and a unique opportunity this year, for a number of reasons. The United States and, in fact, the world is struggling to right a financial system in turmoil, and far, far too many of our fellow citizens are unemployed or under-employed. The number of those around us who lack health insurance, including many people with cancer and cancer survivors, may now have eclipsed 50 million. Even comparatively wealthy communities in the United States are struggling to support those in need. Those survivors who need expensive medicines are challenged, now, more than ever, to find a way to pay for those drugs.

But, as surely as we live in an economically troubled time, we also face a moment of extraordinary scientific opportunity.

On February 17, 2009, President Obama signed into law a sweeping economic recovery plan. The $787 billion bill is called the American Recovery and Reinvestment Act. This legislation is about employment, about creating jobs and preserving jobs and righting the American economy. But it is more. When he signed the stimulus act into law, President Obama said: “… I hope this investment will ignite our imagination once more, spurring new discoveries and breakthroughs in science, in medicine, in energy, to make our economy stronger and our nation more secure and our planet safer for our children.” The President clearly recognizes that the future of our country and the stability of its economy will depend on the creation of new knowledge, of new technologies, of imaginations unleashed.

We are on the threshold of altering the course of this disease for millions of people, young and old alike.

This is no small challenge. Yet it strikes at the very heart of what we do at NCI. We are fortunate to work every day toward a collective goal that cancer will not be the feared diagnosis it is today. We are on the threshold of altering the course of this disease for millions of people, young and old alike.

The bottom line is that NCI is committed to the core belief that how we spend all of the resources we are granted, how we strive for comprehensive plans and strategies must, by their boldness and vision, provide answers that ultimately change the course of the diseases we call cancer; not one disease, but hundreds of diseases. You rightfully expect us to do no less.

I want to share with you the ways the National Cancer Institute is taking up the call: how we have more than just a vision, how we have developed a coordinated action plan to move cancer research forward in innovative ways.

When it became clear that economic stimulus funds would be coming to NCI, we began to carefully consider where $1.3 billion in new resources could do the most good, where the demand was greatest, where our knowledge of the biology of cancer and new technology were leading us. Given that the American Recovery and Reinvestment Act is a once-in-a-lifetime opportunity, we also thought long and hard about what Americans want from all of us. We came back repeatedly in these discussions to the conclusion that they want better ways to prevent cancer and that they want the earliest diagnosis. And most importantly, for those of you who are cancer survivors, you want new therapies with fewer side effects that will turn cancer into a condition you can live with and not die from.

Economic stimulus funds give us the chance to be visionary; to make strides today toward realizing the promise of personalized medicine; to enhance the process of drug development from target identification to translation into viable therapies; to move cancer research from the accumulation of scientifically exciting genomic data to a new way of approaching prevention, diagnosis, and therapy; and to ensure access to our latest science for all.

Within the hopeful and helpful news of greater funding of grants, we must also note the President’s call to “ignite our imagination.” We must not simply see the economic stimulus package as more dollars toward business as usual.

Economic stimulus funds give us the chance to be visionary, ... and to ensure access to our latest science for all.

NCI has outlined signature projects: areas of investigation that are uniquely positioned to accelerate discovery in a short number of years. Among NCI’s signature projects, three key initiatives hold important promise to unlock cancer’s genetically driven pathways and move them forward to first-in-man studies. The nature of much of this work will be focused, team science.

In 2006, NCI and the National Human Genome Research Institute initiated a pilot project designed to accelerate our understanding of the molecular basis of cancer through the application of advanced technologies. Three years later, The Cancer Genome Atlas – or TCGA, as it is better known – has established characterization and sequencing centers, along with programs in data management, bioinformatics, and computational analysis. To date, TCGA has sequenced over 200 tumors in glioblastoma, along with lung and ovarian cancers. Already, in glioblastoma, TCGA has identified three genes not previously associated with this deadly cancer and delineated as many as four subtypes of glioblastoma, to date. With that foundation of success, we plan to move TCGA forward with a goal of identifying all of the relevant genomic alterations in 20 to 25 major tumor types.

In addition, during the past year, NCI has also begun a program in pediatric cancer genomics. TARGET, which stands for Therapeutically Applicable Research to Generate Effective Treatments, will apply next-generation sequencing to at least 100 tumor specimens per childhood cancer.

Programs like TCGA and TARGET – along with numerous other whole-genome association studies using large populations to assess risk – are generating a mountain of data and revealing potential genetic defects that occur within cancer. While scientifically fascinating and intellectually groundbreaking, these data primarily remain raw information that must be developed into knowledge of causal pathways and functional biology. Based on an intimate understanding of these pathways, through the development of new probes and new assays of biologic function, we will convert what is today considered “un-druggable” into functional pathways with clearly defined targets for manipulating those pathways. Moving from data, to function, to target, to therapy will not be simple, nor will it be easy or inexpensive. But NCI is firmly committed to using today’s opportunities to design and construct a personalized cancer care drug development platform, which is the second of NCI’s signature initiatives.

At the beginning of the platform will be functional biology centers: a virtual network of investigators who will take promising genetic alteration identified in TCGA and answer specific questions about biologic function and potential druggable targets.

Another network, the Chemical Biology Consortium, will provide the necessary chemistry and chemists to accelerate the discovery and development of new anti-cancer agents, which NCI will be able to have produced and moved into pre-clinical testing and toxicology.

Hand in hand with the effort to develop a platform for personalized medicine, we need to develop an improved clinical trials system.

In addition, NCI is taking steps to create the first of a small national network of patient characterization centers. Always employing the latest technologies, these facilities will serve wide geographic areas, bringing together genomics and genetics, proteins and proteomics, all in the interest of matching a genetically characterized patient and his or her characterized tumor to appropriate and optimal therapeutic solutions.

This wide-ranging plan will require the contributions of biologists, chemists, informaticians, and clinical scientists who are devoted to a clear path from discovery to patient. That is not only the nature of translation; I believe it will be a model for the study of many diseases and, ultimately, a model of 21st century healthcare, when we are able to match characterized patients and molecularly profiled tumor types to highly specific molecularly targeted therapies.

This platform is a vision for a new way of thinking. But it is not an unrealistic concept. It is an action plan – a blueprint for what we are beginning to assemble this year, making the optimal use of every new resource. It is a blueprint for 21st century translation.

Hand in hand with the effort to develop a platform for personalized medicine, we need to develop an improved clinical trials system to better accommodate the validation of highly targeted therapies and to accurately assess the targeting of those therapies in people in real time. The challenge in translation is optimally matching the tumor and therapeutic recipe. As we move forward, this will be the pattern of treatment for all malignancies.

NCI’s third signature initiative is one that is personally extremely exciting and another bold answer to the President’s challenge that we expand the boundaries of science. Over a year ago, NCI commenced a series of workshops that began to bring aspects of the physical sciences to the problem of cancer. We discussed how physical laws governing short-range and other forces, energy flows, gradients, mechanics, and thermodynamics affect cancer, and how the theories of Darwinian and somatic evolution can better help us understand and control cancer. From those meetings has come the impetus of an idea that is soon to become a network of NCI-supported physical sciences-oncology centers. Working closely with the cancer research community, these centers will foster a team science environment that incubates and tests novel cancer concepts by studying and sometimes challenging accepted scientific dogma. These centers will, I believe, be proof yet again that approaching a difficult scientific problem from a new perspective can advance all research. These new centers will interface exceptionally well with our very successful centers in nanobiology, proteomics, and systems biology.

Cancer is, after all, an old problem, and it is the nature of science to move judiciously and incrementally. Yet today’s pace of discovery – of the genetic basis of disease – is unfolding at a rate never before envisioned. Even so, we must be mindful that our task is far from complete. People still need answers. People still need better treatments, better prevention, and better early detection. We will recommit ourselves to answering your call.

We have many challenges ahead, many discoveries still to be made. We would be wise to follow George Bernard Shaw’s admonition that “Science becomes dangerous only when it imagines that it has reached its goal.” We are undoubtedly moving toward the day when cancers will be diagnosed early and controlled. We will not rest until we have constructed molecular and genetic methods of cancer prevention. We will not rest until we have well and thoroughly prepared those who will take up the fight after we are done.

♦ ♦ ♦ ♦ ♦

This article was published in Coping® with Cancer magazine, July/August 2009.