domingo, 8 de mayo de 2016

Aiming High — Changing the Trajectory for Cancer — NEJM

Aiming High — Changing the Trajectory for Cancer — NEJM


Aiming High — Changing the Trajectory for Cancer

Douglas R. Lowy, M.D., and Francis S. Collins, M.D., Ph.D.
April 4, 2016DOI: 10.1056/NEJMp1600894
For the loved ones we’ve all lost, for the families that we can still save, let’s make America the country that cures cancer once and for all” (President Barack Obama, State of the Union Address, January 12, 2016).
We’re talking about prevention and early detection. I’m convinced we can get answers and come up with game-changing treatments and get them to people who need them. We have an opportunity to fundamentally change the trajectory” (Vice President Joe Biden, University of Pennsylvania Abramson Cancer Center, January 15, 2016).
Cancer is hundreds of diseases. Biomedical research has made it possible to cure some of them, including most cases of childhood leukemia and Hodgkin’s lymphoma, and has spurred significant progress in treating others. Indeed, over the past quarter century, U.S. cancer mortality rates have decreased by 23%, as medicine has saved an estimated 1.7 million lives and prevented immeasurable suffering. Much of this success has been fueled by strong, sustained federal investments in basic, epidemiologic, and clinical research and resulting advances in prevention, screening, diagnosis, and therapy. Yet more progress is urgently needed. Cancer is the second-leading cause of death in the United States and is expected to kill nearly 600,000 Americans in 2016 — about 1600 people every day.
President Obama’s call for a new initiative, led by Vice President Biden, to galvanize research efforts against cancer, is not the first sweeping anticancer campaign ever proposed — indeed, President Richard Nixon unveiled a “War on Cancer” in 1971. So questions have arisen about why such an initiative is needed now and what’s different today from 45 years ago.
We believe the time is right for a renewed surge against cancer because, thanks to the coalescence of new scientific insights and technological innovations, prospects for success are greater than ever. One instrumental advance has been a dramatic shift in our fundamental understanding of cancer. Work using tools and technologies arising from the Human Genome Project and data from the Cancer Genome Atlas and other studies has clarified that cancer is a disease of the genome. It has become increasingly apparent that knowing what driver mutations are present in a particular tumor is often more important than knowing which organ system it arose from. Genomic technology has also shown that although each tumor is molecularly unique, certain pathways are repeatedly affected — findings that have informed the design and use of a new generation of drugs targeting those pathways.
Another rapidly evolving area of inquiry looks beyond tumor cells to other factors, such as stromal and immune cells in the tumor microenvironment that often affect tumor progression. Powerful new bioinformatics tools and methods enable assembly, management, and analysis of very large sets of complex molecular and clinical data, or “big data,” which are necessary for generating predictive models of cancer progression and therapeutic response.
Meanwhile, after a decades-long struggle, strategies for spurring the immune system to attack cancer cells have begun to achieve dramatic successes. Some such immunotherapies, including checkpoint inhibitors and chimeric antigen receptor T-cell therapies, have been shown to induce remissions or even cures in people with treatment-resistant forms of melanoma, leukemia, and lymphoma, as well as late-stage mesothelioma and ovarian, lung, kidney, and triple-negative breast cancers. However, many solid tumors fail to respond well to these approaches, and initially positive responses are not always sustained. There is still much work to do.
Clearly, it will be a monumental challenge to figure out how to apply and build on all the recent advances in our understanding of cancer biology and new therapeutic approaches while also making progress in prevention, screening, and early detection. The new cancer-research initiative aims to make a difference in all these areas by addressing two overarching priorities: increasing the resources devoted to fighting cancer and breaking down silos to unite the cancer-fighting community. Coordination throughout the government is being enhanced by a high-level Cancer Moonshot Task Force involving multiple departments and led by the Vice President.1
Fueled by an additional $680 million in the proposed fiscal year 2017 budget for the National Institutes of Health (NIH), plus additional resources for the Food and Drug Administration, the initiative will aim to accelerate progress toward the next generation of interventions that we hope will substantially reduce cancer incidence and dramatically improve patient outcomes. The NIH’s most compelling opportunities for progress will be set forth by late summer 2016 in a research plan informed by the deliberations of a blue-ribbon panel of experts, which will provide scientific input to the National Cancer Advisory Board.2 Some possible opportunities include vaccine development, early-detection technology, single-cell genomic analysis, immunotherapy, a focus on pediatric cancer, and enhanced data sharing (see tablePotential Opportunities for Cancer Research, Fiscal Year 2017.).
The panel will tap into the expertise of scientists, oncologists, patient advocates, philanthropists, and representatives of the pharmaceutical and biotech industries to focus on emerging frontiers in the understanding and treatment of cancers. New opportunities for collaboration among government agencies and between the public and private sectors are being explored and will be highlighted at a summit in the late spring. We expect these discussions to uncover meritorious and previously unanticipated scientific opportunities to reduce cancer incidence and improve real-world cancer outcomes, including opportunities that seek to narrow or overcome disparities in cancer prevention, screening, and treatment that affect rural, poor, and minority populations.
To maximize the scientific community’s ability to take advantage of these emerging possibilities, the blue-ribbon panel will explore the possibility of establishing an Exceptional Opportunities in Cancer Research Fund to support the pursuit of new ideas addressing currently intractable problems in cancer research. The National Cancer Institute (NCI) could then respond quickly to leverage novel insights in any area of oncology that’s ripe for expansion — from basic science through translational approaches to clinical trials. Such an investment would help to ensure that our country’s most creative scientists have the necessary resources to pursue investigations that may lead to breakthroughs.
A second goal of the initiative will be to overcome barriers that often prevent collaboration and information sharing among the various groups working to defeat cancer and that limit access to state-of-the-art research.3 With leadership from the Cancer Moonshot Task Force, efforts to align the endeavors of government, industry, academia, philanthropy, and patient groups will be amplified. In addition, data and technology innovators will help to revolutionize the ways in which cancer-related data are shared and used to achieve new breakthroughs, and the federal government may seek ways to facilitate data sharing among researchers who are currently reluctant to disseminate their data and results. The NCI’s Cancer Genomic Data Commons and Cancer Genomics Cloud Pilots are both examining new methods to facilitate sharing of data, novel algorithms, software, tools, and annotations, and they provide ways of measuring the impact of such sharing.
Vice President Biden has also made it clear that he wants to take steps to ensure that all Americans — even those who have limited resources or live far from major cancer centers — have access to leading-edge cancer treatment, prevention, and screening approaches. Currently, less than 5% of U.S. adults with cancer take part in clinical trials.4 In addition, community oncologists, who currently treat about two thirds of patients with cancer,5 often have limited access to new research and related advances and face potential financial disincentives to enrolling their patients in trials. Following a participant-centric model being pioneered in the NIH-led Precision Medicine Initiative, the cancer-research effort will be informed by input from the patient community and will ensure that patients and their families are treated as partners, with access to their own health information and opportunities to contribute to research.
Although key actions and deliverables remain a work in progress, one aim of this new initiative is certain: to inspire a new generation of American visionaries to defy the boundaries of current knowledge about cancer. Unleashing the talents of the scientific community by providing a strong, steady stream of resources should enable biomedical research to accelerate progress in the fight against cancer. We expect these efforts to build a firm foundation for the development of better means of prevention, treatment, and cure for all types of cancer.
Disclosure forms provided by the authors are available with the full text of this article at
This article was published on April 4, 2016, at


From the National Cancer Institute (D.R.L.) and the National Institutes of Health (F.S.C.) — both in Bethesda, MD

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