Cancer Progress Report 2011: Contents
Fully Realizing the Potential of Our Current Opportunities
Unquestionably, we stand at a defining moment in our Nation’s commitment to conquer cancer. The explosion of genetic information and our ever-increasing understanding of how to apply it are providing cancer patients with less toxic and more effective treatment options that are forming the foundation and driving our early successes in personalized medicine.
Personalized cancer medicine, also called molecularly based medicine, precision medicine, or targeted therapy, is moving forward rapidly and has already been integrated into clinical care for some forms of cancer. The successes of some of the targeted drugs prove that our deeper understanding of cancer at all levels, particularly the molecular level, can significantly improve patient care.
These advances are a window into a future where all cancer treatment and prevention strategies are based on both a person’s own genetic makeup and the genetic makeup of their specific cancer. This vision of the future will require a great deal of innovation in discovery and clinical research, collaboration across all sectors, and a continued fervent commitment from our Nation to tackle cancer.
What Will It Take to Make Personalized Medicine the Standard of Cancer Care?
A Comprehensive Understanding of Cancer
First and foremost, we must continue to pursue a more comprehensive understanding of cancer at all scales, from molecules to cells to man.
The convergence of genomic sequencing, including sequencing all of the RNA that will make proteins, and information technologies is providing an unprecedented knowledge of the molecular basis of cancer, which is necessary to pinpoint the vulnerabilities within the different cancers. This new knowledge is essential to uncovering the biomarkers that will drive the development of highly effective targeted therapies, predict risk for specific cancers, and allow clinicians to develop individual treatment options and prevention strategies for their patients.
To deepen our understanding of cancer, our Nation must provide the necessary resources for vitally important research, particularly NIH- and NCI-supported cancer research. For example, we must ensure support for the several large-scale tumor sequencing projects that are beginning and will continue to reveal more molecular information about the subtypes of numerous cancers. Information gleaned from these studies accelerates the development of molecularly based biomarkers, diagnostics, and drugs in the private sector. The development and use of combinations of biomarkers called gene signatures will further increase the efficacy of an increasingly precise form of therapy, not only predicting drug response, but also potential harm.
Due to rapid technological advances, many foresee a time, not far from today, when every cancer patient’s tumor will be sequenced prior to treatment. Although necessary, a full genetic understanding of cancer is but one piece of the puzzle. A complete knowledge of cancer at the epigenetic, microenvironment, and systemic levels will also be required in order to see the complete picture.
Our large-scale approaches to probing cancer are producing massive amounts of information that will continue to grow as technologies become increasingly sophisticated. As such, new storage infrastructure, bioinformatics systems, and telecommunications networks are already required to manage our current large data sets, and this need will only increase in the future. It will be necessary not only to manage this increasing volume of information, but also to deliver it to patients and physicians to inform cancer care. Further, the collection and interpretation of this information will only be made possible by multidisciplinary teams of researchers, caregivers in the community, and the patients themselves.
Collaborative Multidisciplinary Teams
Indeed, a more complete picture of cancer will require researchers from the physical, engineering, and mathematical sciences working together with biological and clinical researchers. These multidisciplinary teams represent the convergence of the biological and cancer sciences with the physical sciences, which examine the properties of cancer like thermodynamics, biomechanics, and fluid dynamics in an effort to apply new thinking, computational modeling, and ways of transforming these data into meaningful information regarding cancer cell behavior.
Anticipating the need for the integration of the physical sciences and engineering with the biological sciences, many institutions across the Nation and globally are creating departments that foster collaboration across these once-isolated disciplines. Success in this endeavor will provide even greater opportunities in research, particularly cancer research. We must, however, continue to invest in the training of both current and future generations of researchers to build the multidisciplinary workforce needed to successfully perform this work and yield further advances against cancer.
Although critical to the success of personalized cancer medicine, multidisciplinary teams alone will not be enough. Understanding the multiple complex networks that comprise cancer, ranging from the molecular to the human scale, requires entirely new ways of thinking and models, an approach known as systems biology.
Systems biology is focused on the identification of key networks, pathways within these networks, and interactions among the networks that cells use to function normally. Likewise, systems cancer biology seeks to define how these same networks have been deranged so that they now function to support cancer initiation and development. In the near future, new computational and virtual models will map and integrate information from genomics, proteomics (the study of protein interactions), and epigenomics research, along with clinical data, to predict interacting pathways and specifically identify unstable “nodes” that may serve as new targets for cancer intervention, a concept or approach known as computational medicine. The range of new computational methodologies and theoretical models coming from systems biology and computational medicine will most certainly produce more predictive approaches to cancer prevention and treatment that will inform prevention, detection, diagnosis, and treatment.
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Advanced technologies have catalyzed unparalleled progress against cancer, and in turn, cancer research has driven innovation in every decade since the Nation seriously turned its attention to conquering what is likely to be the most difficult of all the diseases that mankind has or will ever face. Currently, technologies such as whole genome sequencing, advanced imaging, bioinformatics, and computational models are providing opportunities to understand and rationally control cancer, but our continued success will rely on even newer technologies.
Although it is difficult to predict which of the many future technologies or developing areas of research will have the largest impact on cancer research and care, some promising areas are likely to be successful.
One such area that is already having an impact and will likely continue to do so is nanotechnology. This field of science creates and applies new materials with dimensions one million times smaller than a millimeter. By taking advantage of the unique physics of these systems, nanotechnology promises to provide innovative strategies and tools to support molecularly based drug development, drug delivery, highly sensitive and accurate molecularly based diagnostics, and new tools for research, particularly cancer research. Indeed, we have already seen the first glimpses of success with nanotechnology in cancer therapeutics. The FDA-approved drug paclitaxel (Abraxane) is a nanotechnology-based form of the drug taxol used to treat breast cancer.
Another field that promises to greatly inform cancer research and future patient care is stem cells. The significant cellular and genomic heterogeneity of nearly all cancers, even within the same patient, has proven difficult to understand. In fact, it is possible that these distinct cell populations within a given cancer have, in part, fueled drug resistance and made many cancers difficult to treat and control. Stem cells are long-lived cells that can develop into multiple cell types within an organism. Given the behavior of stem cells, it is possible that, for some cancers, stem cells may be the root cause of tumor heterogeneity, resistance to therapy, and tumor dormancy.
Another research area that could significantly contribute to future progress against cancer is cancer metabolism. It has been known for some time that the metabolism of cancer cells is different from normal cells. Researchers have been making progress in understanding and potentially exploiting these differences therapeutically. Interestingly, this area is converging with epigenetics; recent discoveries highlight that several key metabolic enzymes are epigenetically silenced in some cancers. Although in its early stages of exploration, the role of the microbiome, which is the sum total of a person’s microorganisms, is an extremely active area of cancer research. The effect of an individual’s microbiome could resonate throughout the body and have an impact on areas like metabolism and drug availability.
Similarly, progress in our understanding of regions of the genome that do not make proteins but fine-tune the expression of proteins, like non-coding RNAs, are being implicated in the development of cancer. Further, this area has already provided excellent research tools and may provide therapeutic benefits in the near future. Likewise, newer and more accurate experimental models of cancer will improve the accuracy of preclinical development and the speed at which these findings can be translated into novel therapeutics that save lives.
Many of these technologies and areas of research are focused on producing new therapeutics. Continued research into the science behind behavior modification, as well as the non-invasive diagnostic tools and technologies, could revolutionize our cancer prevention efforts and render cancer treatment a thing of the past.
In summary, progress in cancer research has enabled a vision for the future in which we understand cancer at a fundamental level and are able to harness the most powerful of emerging and future technologies, along with new approaches of gathering, managing, and interpreting the wealth of information they will provide to achieve personalized medicine. This future is possible and indeed achievable. The U.S. could make no better choice than to continue to invest the resources needed to ensure that cancer is finally controlled for all of its citizens and the world alike.
Progress Report 2011 Contents