What is Required for Continued Progress Against Cancer?
Cancer Progress Report 2012: Contents
Unquestionably, we stand at a defining moment in our Nation’s ability to conquer cancer. The explosion of new knowledge and the exciting technological advances, along with our ever-increasing understanding of how to apply them, are providing innovative ways to reduce the global burden of cancer. Novel strategies for making further strides in cancer prevention, detection, diagnosis and treatment are now on the horizon. Despite these opportunities, there are many challenges that must be overcome if we are to make a quantum leap forward in our mission to prevent and cure all cancers.
First and foremost, we must continue to pursue a comprehensive understanding of the biology of cancer at all stages—the root causes of its initiation, growth and metastasis—and at all scales, from molecules to cells to humans. We need the complete picture of what is happening within cancer cells at the level of genetics and epigenetics, as well as an understanding of the contributions of other cells in the tumor and its microenvironment. Beyond studying these in isolation, an integrated assessment—generated by an approach known as systems biology—of the tumor and the patient’s response to the tumor is essential to fully understand and contextualize the cancer’s causes, prognosis, vulnerabilities and responses to treatments.
With this comprehensive knowledge in hand, we can build better tools for, and be smarter in, our approaches to preventing, detecting, diagnosing and treating cancer. This vision will require a great deal of innovation, effort and collaboration from all those who care about saving lives from cancer and it will require adequate funding from the federal government and other sources to meet the challenges ahead. We must continue to push forward together, or we risk losing more people like seven-year-old
Evan Lindberg, to this dreadful disease.
It is through research that we advance our understanding of the biological factors involved in cancer. But how we conduct research matters, and increased efforts in strategic areas are necessary to achieve a more efficient cancer research enterprise. Gaining a comprehensive picture of cancer will require new tools, new analytics, new ways of thinking and new ways of working together. These areas, which are described below, span the continuum from improvements in fundamental research to performing clinical research using our healthcare delivery system as a natural laboratory in which research can continue in everyday patient-clinician interactions.
Improved Biospecimen Collection and Repository System
Biospecimens, such as samples of tumors that have been removed from cancer patients, are the backbone of cancer research. A great deal of the current understanding of cancer biology comes from studying the differences between tumor tissue and healthy tissue, between primary tumors and metastases and among different types of tumors. In this way, researchers are able to identify weaknesses to be exploited to potentially kill cancer cells.
Many research questions do not require direct access to patients and can be studied using the patients’ donated biospecimens. If a repository of samples, sometimes referred to as a “biobank” or a “biorepository,” is available to researchers, then hundreds or even thousands of samples can be tested quite rapidly. The utility of research on archival tissue is highlighted by the fact that this strategy has already led to a number of scientific discoveries, including the identification of HCV and the determination that HIV originates from a precursor Simian immunodeficiency virus (SIV), among others. The examination of biospecimens from clinical trial participants is also a promising means to identify drug resistance mechanisms, the knowledge of which can lead to the development of new drugs to overcome such resistance.
Currently, most biospecimens are collected and stored by a variety of institutions, organizations or individual researchers, making them inaccessible to the greater research community. Broader access to the samples would increase their value and accelerate subsequent discovery; this could be achieved by establishing a national repository of high-quality, clinically annotated tissue samples collected using global standards in privacy protection and archiving. Before any such repository is created, universal standards for collection, annotation, cataloging and storage must be agreed upon and adopted. Further, as research is performed using these samples, it will be imperative that the results from any analyses be archived at the appropriate time(s) and identified as associated with the original sample, enhancing continued discovery and decision-making. Here, too, the development and adoption of standards for data formats and sharing must precede the generation of data sets.
Finally, due to advances in genetic testing that have made it possible to link unlabeled biospecimens to individuals, patient privacy and consent are of the utmost importance, and ethical safeguards must also be agreed upon and adopted to ensure that patients are protected.
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Multidisciplinary Team Approaches and Collaboration
Modern science and medicine has taught us that to obtain a comprehensive picture of the complex set of diseases called cancer, it will be necessary to overcome barriers to progress and explore opportunities for new knowledge, new models, and new collaborative partnerships. This means integrating scientific fields, for example immunology and cancer biology, two areas that have historically tended to function independently. It also means bringing in to the cancer research effort the non-biological disciplines, such as physical, chemical, engineering and mathematical sciences, which can provide novel insights into important material properties of cancer.
Advances in technology now allow researchers to generate vast amounts of data. The combination of huge genomic data sets with complex cancer biology has created new opportunities for understanding cancer, but it has also yielded new hurdles and scientific needs. New and more sophisticated analytical methods are required to extract meaning from mountains of numbers and have necessitated the engagement of experts in the fields of informatics and computational biology.
For multidisciplinary teams to be effective and yield new advances against cancer, we must invest in the training of both current and future researchers so that they are able to work productively within this new team environment. Also, one of the most important things to learn is how to communicate effectively across research disciplines, each with its own jargon and scientific foci. Developing successful teamwork skills requires learning to work across disciplines and academic departments and the knowledge of how to cooperate across states, regions and continents.
Successfully translating research into effective cancer interventions requires more than just dedicated and talented researchers. Along the journey from scientific discovery to intervention is a wide variety of stakeholders, including members of academia, funders, regulators, the biotechnology and pharmaceutical industries, philanthropic organizations, patient advocacy groups and the patients themselves.
One type of partnership that provides an interesting opportunity to drive future innovation and accelerate productivity while reducing the cost of research and development is precompetitive collaboration, which refers to the sharing of research findings that have traditionally been considered proprietary commercial assets (e.g., genomic data sets or clinical trial comparator arm data) between financially distinct companies, organizations and institutions; see Sidebar on
Equally important are academia-industry collaborations and public-private partnerships, such as the Structural Genomics Consortium, an open-access database of the structures of biomedically relevant proteins that includes several large pharmaceutical companies among its members and financial backers. To encourage more cooperation of this nature across the sectors, it will be necessary to provide support and encouragement, such as tax incentives, funding and/or policy changes, to those who actively participate.
Effective collaborations between regulators and those involved in the drug development process is also required to speed the delivery of new treatment approaches to patients with cancer. Among the many issues that must be resolved in the near future are regulatory policies and incentives that allow multiple companies to test investigational targeted agents as therapeutic combinations in a single clinical trial. Although these efforts have begun and several companies are moving forward in a collaborative testing of this nature, many obstacles remain to be addressed. The rapid pace of innovation in cancer science and medicine requires that there be ongoing, robust communications between the FDA and the scientific community. This is essential to ensure the seamless integration of science into the regulatory process.
Improved Approaches to Clinical Trials
Clinical trials are a central component of cancer research, as they are the only way for therapies that show promise in laboratory studies to be translated into treatments that extend and improve the lives of cancer patients. It typically takes many years for cancer clinical trials to determine the safety and efficacy of a particular treatment. If we are to accelerate this process for the benefit of cancer patients, all stakeholders must work together to overcome the obstacles that are preventing the conduct of faster, more efficient clinical cancer trials.
Low participation in clinical trials by adult cancer patients leads to delays in completion or even trial termination, which is a major hurdle that all clinical trials must be address. In fact, fewer than 5% of adults diagnosed with cancer participate in a clinical trial, despite the fact that clinical trials are an opportunity to receive the newest and potentially most innovative treatments for their disease. Low participation is even more pronounced in underserved, minority and advanced-age populations, leading to concerns about the applicability of trial results to these subgroups. The reasons why patients do not participate in clinical trials include, but are not limited to, the lack of patient awareness; lack of physician awareness, encouragement or engagement in the research enterprise; fear of adverse side effects; bothersome trial requirements; ineligibility; and language or cultural barriers.
One of the greatest challenges in clinical trials is accruing enough patients to statistically prove that a given therapy has had an effect. To confirm a small, but significant therapeutic effect, a large number of patients must be enrolled in a given clinical trial to be sure that observed differences in outcomes are due to the effects of the therapy and not due to chance. Having a greater number of patients on trial translates to more time and increasing costs. One approach to accelerate the speed with which a clinical trial reaches a conclusion about the value of a new therapy is to enroll only those patients most likely to benefit from the treatment being tested. To achieve such a selective cohort, we need to identify biomarkers that predict a patient’s chance of responding to the investigational therapy, such as having a mutation that will be targeted by the drug being tested. A benefit of this selective strategy is that patients unlikely to respond to the therapy will not be enrolled and, therefore, will avoid exposure to unnecessary side effects. Furthermore, trials with preselected cohorts require fewer patients because the effects of the drugs will not be averaged across responders and non-responders alike. Identifying biomarkers for subpopulations who respond is challenging, and new trial designs are being implemented to combine biomarker discovery and validation with the development of new drugs. Many scientific and policy issues must be considered for these new trial designs.
Another way to speed the drug development process is to reduce the length of time it takes to complete a clinical trial. The preferred endpoint used in clinical trials to determine that a cancer treatment’s efficacy is overall patient survival, which is often only measurable after a period of several years. As such, it can take a long time to obtain definitive results of clinical trials. Surrogate endpoints that can be measured in less time than overall survival, such as progression-free survival, disease-free survival and tumor response (assessed by advanced imaging technologies, for example) are increasingly being used. To use surrogate endpoints to speed the drug development process, researchers must first prove that positive short-term surrogate endpoints actually lead to the intended long-term outcome (i.e., extended overall survival). Regulators who evaluate clinical trials must also agree on the relevance of such surrogates; therefore, interactions between clinical researchers and regulators are critical to the further development and approval of these endpoints to bring about prompter clinical trial conclusions.
Adoption of Learning Healthcare Systems
The community that conducts cancer research and the community that implements the practical results of those findings in everyday clinical settings have all too often been poorly connected. As a result, the flow of research information can be unidirectional, from researchers to practitioners. Yet, there is much to be learned from the everyday care of patients if the appropriate data is collected about treatments and outcomes. Widespread adoption of electronic medical records (EMRs) will make it possible to more easily access and compile such clinical data. It will be essential to ensure that EMRs include standardized data fields sufficient to catalyze secondary research and foster the flow of empirical observations to drive new research questions. These data represent a previously untapped research resource and provide evidence created in settings that are representative of community care. Recently, there has been growing emphasis on reducing the separation between the research community and the clinical care community to take advantage of the vast amount of data collected during routine care to improve patient care. Care delivery systems that can actively contribute to research and improve the delivery of care are referred to as “learning healthcare systems” (see Sidebar on
Learning Healthcare Systems), and these will be vital to ensuring that therapies that help patients in theory actually help them in practice.
We are rapidly moving towards a future in which we understand cancer at a fundamental level. We are able to harness emerging technologies—along with new approaches of gathering, managing and interpreting the wealth of information they will provide—to achieve a world free from cancer. The U.S. could make no better choice than to continue to invest the resources needed to ensure that cancer is finally conquered for all of its citizens and the world alike.
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Progress Report 2012 Contents