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NCI Director Dr. Andrew von Eschenbach spoke to the attendees of the IMF Patient-Family Seminar on the evening of June7, 2002 at Tysons Corner, VA. He highlighted his vision of the furture of cancer research and how it relates to myeloma patients.

The following is an excerpt from Dr. von Eschenbach's speech.

"Good evening. Just for a few minutes, I want to depart from my prepared remarks. The night before the Senate hearing, I was briefing the Secretary for his presentation on the panel that immediately preceded Susie’s. I knew who was going to be on the second panel, and I was wondering, "Who is this Susie?" Well, now I know!

"I don’t think I fully appreciated why I was coming here until a few minutes ago. What I’ve learned in the last hour or so is how important it is for you to talk to me. How important it is for me to see your passion, your commitment, your resolve, your pain. How important it is for me to be reminded of why I am privileged to be the director of the National Cancer Institute. I’ve been privileged in a variety of ways throughout my career, but I have also been privileged to understand and "walk the walk," as I am also a two-time cancer survivor. We’re in this together.

"I want to share with you a message of new hope and renewed hope that there is within our grasp an opportunity to truly, fundamentally change the face of cancer. I want to share with you a concept that I refer to as "strategic inflection." This issue of strategic inflection has implications specifically for multiple myeloma, and, as you’ll see, is a paradigm for the entire arena of cancer. There are enormous possibilities, and the realization is only going to come about through partnerships.

"We are beginning to be able to understand cancer at its basic biomedical and biological level. We have arrived in biology at that strategic inflection. I borrow that term from Andy Grove, who in his book Only the Paranoid Survive, refers to it as an event when change is absolutely profound; what he calls a 10X change.

"In his own particular area he gave this example: the introduction of the microprocessor. Those who understood its implications rode the expediential curve and the others went into decline. We are at a strategic inflection in oncology. If you think back to the turn of the 20th century, the fundamental quest of science was to understand the nature of matter. Physics was the queen of sciences. Our focus was on the atom and unlocking the secrets of the nucleus. When we accomplished that, we created a strategic inflection that changed the course of civilization. Almost eradicated civilization—but fundamentally changed it.

"At the turn of the 21st century, almost one hundred years later, our focus in science has changed from understanding the nature of matter to understanding the fundamental nature of life. We have shifted from physics to biology, molecular biology and genetics. Instead of unleashing the secrets of the nucleus of the atom, we are unraveling the secrets of the nucleus of the living cell. This has placed biology at the point of strategic inflection.

"The funding Susie was pleading for in her address to Congress is an investment that could change not only our ability to deal with cancer, but with a whole host of diseases in which there are degenerative changes. For the first time, we have begun to understand cancer at the genetic, molecular, and cellular level. This has begun to create a whole shift in our approach to cancer. Today the transition is away from "seek and destroy" to the phenomenon of target control. We now understand the mechanisms that result in a normal cell becoming a malignant cancer cell.

"The other thing that is apparent to us is that this process of malignant progression involves very discreet steps that are biologically controlled. In order for a cancer cell to succeed in its mission, it has to be able to effectively compete in a variety of events—growth, invasion, metastasis, resistance to therapy. We can begin to think of not necessarily having to destroy the cancer but of controlling it and preventing it from being able to succeed in any one of those steps along the way. We begin to see, in this new paradigm, that cancer can be quite vulnerable because there are multiple places where we can successfully intervene and stop, impede, or impair its progress.

"We have gained ground on cancer, but it’s clear that we have not even begun to scratch the surface in terms of what we must achieve. You know this from the perspective of myeloma and the tragedy that this disease carries with it. Our challenge is great, but our possibilities are even greater. Our paradigm of the past was to see the tip of the iceberg and use our traditional weapons—surgery, chemotherapy, and radiation—to try to destroy it. Now we can look below the surface and see the fundamental processes that are giving rise to the cancer and attack them individually and collectively. All this is coming at almost breakneck speed because of our incredible evolving knowledge and the advances in technology.

"One of the obvious advances that has occurred in multiple myeloma is the recognition of the important role of growth factors. One of the most important drugs that has occurred in treatment—in blocking of angiogenesis, or the development of abnormal endothelial cells and blood vessels—is thalidomide. This has had obvious benefit in multiple tumors, particularly in myeloma. The other very important breakthrough is our understanding of the role that NF Kappa B plays as an accelerator in the malignant process. A drug has been developed that is a proteasome inhibitor, PS341. Using it, myeloma cells appropriately undergo programmed cell death or apoptosis.

"Once the mechanism was understood, these biologic-based interventions became available as effective modalities of treatment. We need to promote and exploit, through research, our understanding of these mechanisms. Cancer is an extraordinarily complex problem. We have only begun to scratch the surface in our understanding of its underlying biology, but these breakthroughs have provided us with new opportunities, and we need to make sure that the breakthroughs and the understanding continue.

"Our delivery process, particularly through clinical trials, continues to be an important part of the NCI agenda. We must maintain a work force that can discover, create, and deliver. Our training programs will continue to be emphasized. We are also looking at promoting and developing alternative disciplines that are going to be necessary to drive this new paradigm—disciplines that have not normally been part of the traditional mainstream of biology-based interventions. The underlying drive is a strategy I would like to create over the next months, and that is the strategy of systems biology and seamless oncology.

"Systems biology investigates each component of the mechanism, but recognizes that the cancer cell does not exist in a vacuum. It exists in a person, and that is as important to the equation as the cancer cell itself. We must begin to emphasize our understanding of the person with cancer in terms of host factors. There are a variety of host factors that enable or empower a patient to combat and cope with cancer that are poorly understood. With the cancer cell itself, we pay a great deal of attention to the genetic and molecular pathways and cell-cell interactions; with regard to the person, we understand a host of factors that have an impact on the outcome of the tumor, particularly the very important issues relating to survivorship. The interaction of the environment with individual host factors, as well as the ability to understand our impact on populations that are at risk, will be an extremely important part of the agenda.

"Seamless oncology means that we go from patient observation to the laboratory and back to the patient in a continuous process. This will allow us to see the effect of biologic interventions on patients and use that information to reinform our investigations, enabling us to keep the engine of discovery and delivery operational.

"I don’t think you need to be a cancer survivor to be a dedicated researcher, but it sure gives you a sense of urgency. I share with you that sense of urgency. We have priorities that will have a specific impact on multiple myeloma. The idea of understanding genomic instability that gives rise to the evolution of tumors, gene-environmental interaction, stem cell research, and particularly important, the effect of public-private partnerships on the acceleration of drug development, are priorities for the NCI that will have a direct effect on multiple myeloma. There are a number of new projects underway at the NCI that will specifically benefit the areas of research that you are interested in and we will continue to develop and nurture those as well.

"The NCI plays a critically important role in fostering and developing research. But the fact of the matter is, no matter how big our budget, the NCI cannot do it alone. My commitment is to collaboration and partnership. Discovery does not reach its full benefit until it actually results in the development of an intervention that can be applied to a patient and save a life. I believe we can seize the opportunity of recognizing how our privilege and our purpose are interconnected. There are extraordinary possibilities within our grasp, and if we can work collaboratively and cooperatively, we can make the dream of a world free of pain and suffering and death due to cancer a reality. We can do it in our time. One hundred years ago they unlocked the mysteries of the atom, and by doing so saved the world from a disaster that was war. We have the same opportunity to use our knowledge of the living cell to eliminate the diseases that result because of cell abnormalities. It is within our grasp to make that happen. Conquering cancer is a reality within our grasp, and it is now our time to seize that reality.

"Thank you for the privilege of being with you tonight, and for the reminder of why I must do what I have been called to do, and how important it is to be of service to you."