Return to Previous Page

Changing the Conversation

National Cancer Institute Annual Progress Report 2011


Knowledge image

Advances over the past decade of cancer research have fundamentally changed the conversations that Americans can have about cancer. Although many still think of it as a single disease affecting different parts of the body, research tells us – through new tools and technologies, vast computing power, and new insights from other fields – that cancer is, in fact, a collection of many diseases whose ultimate number, causes, and treatment represent a challenging biomedical puzzle. Yet cancer’s complexity also provides a range of opportunities to confront its many manifestations.

We now know that cancer is a disease caused by changes in a cell’s genetic makeup and its programmed behavior. Sometimes these changes are spontaneous, and sometimes they arise from environmental triggers, such as ultraviolet radiation from sunlight or chemicals in tobacco smoke, or from behavioral triggers. We have at hand the methods to identify essentially all of the genomic changes in a cell and to use that knowledge to rework the landscape of cancer research, from basic science to prevention, diagnosis, and treatment.

This knowledge brings us – and our national conversation – to a crucial opportunity for acceleration in the study of cancer and its treatment. The emerging scientific landscape offers the promise of significant advances for current and future cancer patients, just as it offers scientists at the National Cancer Institute (cancer.gov) – and in the thousands of laboratories across the United States that receive NCI support – the opportunity to dramatically increase the pace of lifesaving discoveries.

We have at hand the methods to identify essentially all of the genomic changes in a cell and to use that knowledge to rework the landscape of cancer research.

As proof of the increased pace, the trajectory of cancer deaths reflects real and sustained reductions over the past decade or so for numerous cancers, including the four most common: breast, colorectal, lung, and prostate. We have identified proteins and pathways that different cancers may have in common and represent targets for new drugs for these and many other cancers – since so often research in one cancer creates potential benefits across others. And we have made great strides in strategies to prevent cancer (such as quitting smoking and limiting hormone replacement therapy) and to detect cancer earlier, when treatment is more effective and outcomes more favorable.

Then what, specifically, are some of the areas of study that NCI is focusing on? Primarily, cancer is a disease of cells gone awry, of uncontrolled proliferation, of the loss of normal patterns of cell behavior. Cancer arises from a series of genetic and epigenetic changes that endow the cancer cell with its malignant behavior. During their transformation from normal to cancer, tumor cells undergo a large number of key changes. At the simplest level, cancer cells divide at inappropriate times. They don’t respond to the stop and go signals that normal cells do. In their development into tumors, they acquire a range of characteristics that help them survive, proliferate, invade, and grow. These changes include the production of new blood vessels (angiogenesis) to bring needed nutrients for continued tumor growth, and also include physiological actions that block the body’s attempts to get rid of cancerous cells through immunological responses. The tumor develops into what researchers now realize is essentially a new tissue – perhaps even analogous to a new organ – becoming a complex mixture of tumor and normal cells in the tumor microenvironment that help support the existence and continued proliferation of the embedded cancer cells. And, most devastatingly, cancer cells learn to move from their initial home to new, sometimes distant, sites in the body.

Despite these complexities and challenges, scientists now have a rapidly growing knowledge of the biology of a vast array of cancers, across a wide range of sites, both in solid tissue and in blood.

The study of cancer biology must be as diverse as the stages of tumor development and the panoply of diseases being studied. Understanding the biology of cancer requires intensive work at the laboratory bench, in the cold room, at the computer, and at the blackboard. It utilizes such diverse tools as cells grown in culture, frozen human tissues, and organisms as simple as fruit flies or yeast. It involves dialogues and conversations, in person and in the scientific literature. NCI’s cancer biology research – initiated largely by investigators in hundreds of NCI-funded laboratories across the U.S. – helps build the basic knowledge of normal and cancerous cells, developing an ever-deeper understanding of biological mechanisms that may provide the basis for clinical applications to follow. We support and coordinate research projects at NCI and at universities, hospitals, research foundations, and businesses across the U.S. and abroad.

This lofty mission starts with the simplest of questions: What is – and isn’t – normal? From such deceptively simple questions, the study of cancer biology builds the foundation for progress in cancer prevention, screening, diagnosis, and treatment.

One of our most significant initiatives involves studying the genetic underpinnings of cancer. Near the end of 2005, NCI and the National Human Genome Research Institute announced plans for an intriguing new initiative. Each committed $50 million over several years to what would be a pilot project, designed to determine whether large-scale sequencing, followed by intricate analysis and characterization, could accelerate understanding of the molecular basis of cancer. It was an ambitious undertaking, conducted through a network of more than 150 researchers at dozens of institutions across the nation. The first types selected for study were brain, ovarian, and lung cancers.

Fewer than three years after its announcement, The Cancer Genome Atlas (TCGA, as it was nicknamed) delivered its first results. In glioblastoma multiforme, the most common – and deadly – form of brain cancer, TCGA researchers identified three previously unrecognized mutations that occur in the disease with significant frequency, along with core pathways that are disrupted in glioblastoma. The results, based on the genomes of 206 patients, also pointed to a potential mechanism of resistance to a chemotherapy drug commonly used in glioblastoma. A follow-up finding from this study, announced in 2010, showed that glioblastoma is not a single disease, but appears to be four distinct molecular subtypes, each susceptible to different treatments. This knowledge has potential, over time, to lead to therapies better tailored to each subtype.

TCGA’s science is providing the catalyst for further research that holds promise to affect the treatment of many forms of cancer – beginning with the knowledge of its genes and how they go wrong. TCGA’s plan for the next few years is as ambitious in today’s environment as it was at the beginning: sequence, characterize, and understand the genomic changes of 20 or more additional tumor types.

We reap the rewards of investments in cancer made over the past 40 years or more, even as we stake out a bold investment strategy to realize the potential we see so clearly. No matter what the fiscal climate, NCI will strive to commit the resources necessary to bring about a new era of cancer research, diagnosis, prevention, and treatment.

As proof of the increased pace, the trajectory of cancer deaths reflects real and sustained reductions over the past decade or so for numerous cancers, including the four most common: breast, colorectal, lung, and prostate. We have identified proteins and pathways that different cancers may have in common and represent targets for new drugs for these and many other cancers – since so often research in one cancer creates potential benefits across others. And we have made great strides in strategies to prevent cancer (such as quitting smoking and limiting hormone replacement therapy) and to detect cancer earlier, when treatment is more effective and outcomes more favorable.

Then what, specifically, are some of the areas of study that NCI is focusing on? Primarily, cancer is a disease of cells gone awry, of uncontrolled proliferation, of the loss of normal patterns of cell behavior. Cancer arises from a series of genetic and epigenetic changes that endow the cancer cell with its malignant behavior. During their transformation from normal to cancer, tumor cells undergo a large number of key changes. At the simplest level, cancer cells divide at inappropriate times. They don’t respond to the stop and go signals that normal cells do. In their development into tumors, they acquire a range of characteristics that help them survive, proliferate, invade, and grow. These changes include the production of new blood vessels (angiogenesis) to bring needed nutrients for continued tumor growth, and also include physiological actions that block the body’s attempts to get rid of cancerous cells through immunological responses. The tumor develops into what researchers now realize is essentially a new tissue – perhaps even analogous to a new organ – becoming a complex mixture of tumor and normal cells in the tumor microenvironment that help support the existence and continued proliferation of the embedded cancer cells. And, most devastatingly, cancer cells learn to move from their initial home to new, sometimes distant, sites in the body.

Understanding the biology of cancer requires intensive work at the laboratory bench, in the cold room, at the computer, and at the blackboard.

Despite these complexities and challenges, scientists now have a rapidly growing knowledge of the biology of a vast array of cancers, across a wide range of sites, both in solid tissue and in blood.

The study of cancer biology must be as diverse as the stages of tumor development and the panoply of diseases being studied. Understanding the biology of cancer requires intensive work at the laboratory bench, in the cold room, at the computer, and at the blackboard. It utilizes such diverse tools as cells grown in culture, frozen human tissues, and organisms as simple as fruit flies or yeast. It involves dialogues and conversations, in person and in the scientific literature. NCI’s cancer biology research – initiated largely by investigators in hundreds of NCI-funded laboratories across the U.S. – helps build the basic knowledge of normal and cancerous cells, developing an ever-deeper understanding of biological mechanisms that may provide the basis for clinical applications to follow. We support and coordinate research projects at NCI and at universities, hospitals, research foundations, and businesses across the U.S. and abroad.

This lofty mission starts with the simplest of questions: What is – and isn’t – normal? From such deceptively simple questions, the study of cancer biology builds the foundation for progress in cancer prevention, screening, diagnosis, and treatment.

One of our most significant initiatives involves studying the genetic underpinnings of cancer. Near the end of 2005, NCI and the National Human Genome Research Institute announced plans for an intriguing new initiative. Each committed $50 million over several years to what would be a pilot project, designed to determine whether large-scale sequencing, followed by intricate analysis and characterization, could accelerate understanding of the molecular basis of cancer. It was an ambitious undertaking, conducted through a network of more than 150 researchers at dozens of institutions across the nation. The first types selected for study were brain, ovarian, and lung cancers.

Fewer than three years after its announcement, The Cancer Genome Atlas (TCGA, as it was nicknamed) delivered its first results. In glioblastoma multiforme, the most common – and deadly – form of brain cancer, TCGA researchers identified three previously unrecognized mutations that occur in the disease with significant frequency, along with core pathways that are disrupted in glioblastoma. The results, based on the genomes of 206 patients, also pointed to a potential mechanism of resistance to a chemotherapy drug commonly used in glioblastoma. A follow-up finding from this study, announced in 2010, showed that glioblastoma is not a single disease, but appears to be four distinct molecular subtypes, each susceptible to different treatments. This knowledge has potential, over time, to lead to therapies better tailored to each subtype.

TCGA’s science is providing the catalyst for further research that holds promise to affect the treatment of many forms of cancer – beginning with the knowledge of its genes and how they go wrong. TCGA’s plan for the next few years is as ambitious in today’s environment as it was at the beginning: sequence, characterize, and understand the genomic changes of 20 or more additional tumor types.

We reap the rewards of investments in cancer made over the past 40 years or more, even as we stake out a bold investment strategy to realize the potential we see so clearly. No matter what the fiscal climate, NCI will strive to commit the resources necessary to bring about a new era of cancer research, diagnosis, prevention, and treatment.

♦ ♦ ♦ ♦ ♦

Since 1994, the National Cancer Institute has written the Annual Progress Report for Coping’s July/August Celebration issue.

This article was published in Coping® with Cancer magazine, July/August 2011.