Cancer Moonshot 2.0 sets ambitious goals for reducing the United States’ cancer burden
Cancer researchers and clinicians have their eyes aimed at the moon again after President Joe Biden announced a reignition of the Cancer Moonshot in February. Dubbed “Cancer Moonshot 2.0,” this new effort set two ambitious goals: to decrease the age-adjusted death rate from cancer by at least 50% in the next 25 years, and to improve the experience of people and their families living with and surviving cancer.
For context, in its 2022 Cancer Facts & Figures report, the American Cancer Society reported that the cancer death rate for men and women decreased 32% from 1991 to 2019.1
“Looking at the progress that we have made over the past 20-plus years, we have reduced the cancer death rate by about half of this goal,” said Edjah K. Nduom, MD, FAANS, associate professor in the Department of Neurosurgery at Emory University School of Medicine, Atlanta, Georgia, who was selected to introduce President Biden at the unveiling of the Cancer Moonshot relaunch. Dr. Nduom is a neurosurgical oncologist at Winship Cancer Institute of Emory University whose research focuses on ways to harness the power of the immune system to fight brain tumors, like the type President Biden’s son Beau died from in 2015.
“This new effort will attempt to reduce the cancer death rate even faster,” said Dr. Nduom. “That is something I think people can get behind.”
A Look Back
Cancer Moonshot 2.0 is the most recent entry in the long list of national efforts to reduce cancer deaths. One of the first crucial moments was President Richard Nixon signing the National Cancer Act in 1971, which celebrated its 50th anniversary last year.
“I remember well in the 1970s when Time and other similar publications wrote about the idea that there would be a ‘magic bullet’ in the war against cancer,” recalled Joseph Alvarnas, MD, vice president for government affairs at City of Hope, a cancer research and treatment organization in Duarte, California, and chief clinical advisor at AccessHope, a subsidiary of City of Hope. “There was a belief that it would be simple, and cancer would be easy to conquer.”
As history has shown, that did not turn out to be the case.
“What we found was the genetic underpinning of cancer, and we were able to really describe the underlying complexity that far exceeded what any of us would have guessed,” Dr. Alvarnas said. “Our greatest cancer success came in figuring out this underlying biology and learning how to target it.”
The seminal achievement in this area was the development of the BCR-ABL tyrosine kinase inhibitor (TKI) imatinib for the treatment of chronic myeloid leukemia (CML). According to Dr. Alvarnas, this drug pointed to a future in which genetic knowledge could completely change what a cancer diagnosis meant to real people.
In his last State of the Union Address in 2016, President Barack Obama announced a national effort to cure cancer, the original Cancer Moonshot. This effort was designed to support biomedical research to accelerate a cure for cancer using the variety of new scientific insights and technologies developed in recent decades, including targeted therapies. As vice president, Biden was tasked with guiding the effort to achieve three goals: accelerate scientific discovery in cancer, foster greater collaboration, and improve sharing of data.2
“The Cancer Moonshot had an auspicious goal of gathering 10 years of knowledge in five years’ time by making investments where possible and allowing scientists to bring their innovations to bear,” Dr. Alvarnas said.
The investments were significant: from 2017 to 2022, more than $1 billion in funding has supported 240 research projects across more than 70 cancer science initiatives.3 Specifically, Moonshot projects have advanced knowledge of immunotherapy through creation of the Immuno-Oncology Translational Network (IOTN) and advanced childhood cancer research with the National Cancer Institute (NCI) Pediatric Immunotherapy Discovery and Development Network (PIDDN), part of the National Institutes of Health (NIH), and NCI’s My Pediatric and Adult Rare Tumor Network (MyPART).
“We have made significant gains for some resistant and hard-to-treat cancers with immunotherapy, led by immune checkpoint inhibitors,” Dr. Nduom said. “Moonshot helped create additional immunotherapy networks, link cancer centers, and accelerate clinical trials to fight cancers that had not yet been effectively treated with immunotherapy.”
For example, the Human Tumor Atlas Network (HTAN), an NCI-funded Moonshot Initiative, has developed best practices for tissue and biospecimen collections and storage, as well as policies for sharing data and samples. The Moonshot supported research to reduce cancer risk and cancer disparities through expanded use of proven strategies for prevention and early detection.
Another focus was development of patient-centered networks, as seen with NCI-CONNECT (Comprehensive Oncology Network Evaluating Rare CNS Tumors). Through NCI-CONNECT, patients with rare tumors of the central nervous system can learn about their cancers and find referrals to experts and studies.
“It tries to bring patients with rare tumors together to talk with experts and includes webinars where we can bring together people studying these rare tumors to accelerate progress,” Dr. Nduom explained. “The original Moonshot put us on a good trajectory,” he said. “The new one will work toward more targeted and aggressive goals.”
Prevention and Detection
One of the main strategies for achieving the goals of Moonshot 2.0 is prevention and earlier diagnosis of malignancies.
“We know that, as a result of the pandemic, cancer screening has dropped. In many cancer communities, it has dropped by as much as 90%,” Dr. Alvarnas explained. “We need to get back on track with those cancers that can be screened for using methods like mammography, Pap smears, low-dose computed tomography for people with a history of smoking, colonoscopies, and other targeted screening procedures.”
Earlier diagnosis also means deploying new screening technologies, according to Dr. Alvarnas.
President Biden’s outline mentions such strategies as harnessing the potential of liquid biopsy to detect cancers through blood tests. Tests measuring circulating tumor cells in the bloodstream have been of interest for decades, but more recently, studies are showing these tests may be ready for mainstream use.
Recently, researchers from the Compendium of Cancer Genome Aberrations (CCGA) assessed the performance of a targeted methylation analysis of circulating cell-free DNA to detect and localize multiple cancer types. Results published in 2020 showed that the test was able to detect more than 50 cancer types across metastatic and nonmetastatic stages “with specificity and sensitivity performance approaching the goal for population-level screening.”4 The test, called Galleriâ (GRAIL, LLC), is now commercially available—though not yet approved by the US Food and Drug Administration (FDA)—and recommended for adults with an elevated risk of cancer, including those aged 50 or older.5 The potential for technologies like liquid biopsy for early detection of hematologic malignancies is less clear.
“We already have some markers in the blood for the detection of certain hematologic malignancies like monoclonal spike for development of monoclonal gammopathy of undetermined significance or B cells carrying t(14;18) translocation, which is a hallmark of follicular lymphoma,” said Gilles Salles, MD, chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center. “For these slow-
developing diseases, we lack indicators of who will and will not develop disease.”
Dr. Salles said the question of whether circulating tumor DNA could allow further discrimination of the presence of certain mutations potentially associated with early development of disease remains to be answered.
“The community researching lymphoid disorders are focusing their efforts on better classifying different subtypes of lymphoma to develop more targeted therapies for these patients,” Dr. Salles said. “Liquid biopsy could be used at prognosis to identify patients who need more innovative or aggressive treatment.”
Liquid biopsy can also be used for post-treatment surveillance for the early identification of patients whose disease has relapsed before they start to show symptoms. Use of this technology is currently limited to a few expert centers, Dr. Salles said. “We have to further demonstrate how adapting therapy or screening patients for optimal therapy can be routinely implemented,” he said. “I think it is realistic to say that we can reach that goal in a few years.”
Addressing Inequities
As part of its agenda, the Biden administration said that expanding access to health care by lowering medical costs and expanding insurance coverage is a priority of his administration.6 To accomplish these goals, the administration proposes strengthening the Affordable Care Act (aka, Obamacare), reducing premiums, covering the uninsured in states that did not expand Medicaid, and cutting prescription drug costs. Addressing inequities is also one of Moonshot 2.0’s strategies to reduce cancer mortality and improve the experience for people with cancer.
Disparities in cancer care are abundant and must be addressed, Dr. Nduom said. Research has documented differences in the incidence, prevalence, mortality, survival, morbidity, survivorship, financial burden, screening, and stage at diagnosis across racial and ethnic groups.
Statistics for NCI’s Surveillance, Epidemiology, and End Results (SEER) Program have identified several disparities, including higher mortality rates for many cancer types among Black people, a higher breast cancer mortality rate among Black women, and higher rates of liver and intrahepatic bile duct cancer among American Indians/Alaska Natives compared with the overall population. These disparities are not limited to racial or ethnic groups. There are also higher rates of colorectal, lung, and cervical cancers in rural Appalachia, higher likelihoods of premature death from colorectal cancer among people with lower education levels, and higher rates of smoking and alcohol consumption—which are linked to cancer risk—among lesbian, gay, and bisexual youth.7
“If you simply get the entire population to have similarly low rates of cancer mortality—including the underserved or underrepresented—you would see a huge reduction,” Dr. Nduom said.
To address some of these disparities and move closer to equalizing outcomes in different patient populations, Dr. Alvarnas noted that City of Hope worked to pass the first-of-its-kind Cancer Patients Bill of Rights in California. “Fundamentally, it included the right of patients to have access to care expertise,” Dr. Alvarnas said. “This means that every person diagnosed with cancer has the same ability to access the best care technologies that have been produced.”
Leveraging Precision Medicine
Another important objective of Moonshot 2.0 is “to target the right treatments to the right patients.”
“This goal acknowledges the centrality and importance of precision medicine as a path forward toward better care outcomes and better quality of life for patients,” Dr. Alvarnas said. “Unless we fully leverage the technologies that brought us targeted therapies and even more effective genomic testing, we will undermine the ability to address the needs of cancer patients diagnosed not just today, but those diagnosed tomorrow.”
In the context of hematologic malignancies, Dr. Salles said liquid biopsies may help move the needle forward in precision medicine. For example, in diffuse large B-cell lymphoma, different molecular defects have helped define distinct molecular entities.
“Right now, analyzing those molecular defects requires a tumor biopsy, but a biopsy is not always practical,” Dr. Salles said. “The biopsy may be paraffin-embedded or is not necessarily available at the treatment center.”
In addition, there is heterogeneity in tumors that have manifested in different locations.
“There may be subclonal evolution in some locations; if we only analyze the tumor in one region, we may miss abnormalities present in other regions,” Dr. Salles said. “The advantage of using liquid biopsy is that what is collected in plasma will reflect the different localizations of the tumor.”
Additional Aid
To aid its mission, Moonshot 2.0 will mobilize the entire government, according to a White House statement. Among the planned actions are reestablishing White House leadership with a White House Cancer Moonshot coordinator in the executive office.
A Cancer Cabinet will be convened to bring together departments and agencies from across the government to address cancer on multiple fronts. This could include representatives from the NCI, FDA, Department of Health and Human Services, Department of Veterans Affairs, NIH, and many other entities.
To focus on access, the NCI will organize an effort by NCI-Designated Cancer Centers and other networks such as the NCI Community Oncology Research Program (NCORP) to “offer new access points to compensate for millions of delayed cancer screenings due to the pandemic.”
The White House also plans on hosting a White House Cancer Moonshot Summit to bring together agency leadership, patient organizations, biopharmaceutical companies, and the research, public health, and health care communities.
Missed Opportunities
The goals of Cancer Moonshot 2.0 are lofty, and even with wide-reaching support, they will be challenging to meet. Nicholas Freudenberg, DrPH, distinguished professor of public health at City University of New York’s School of Public Health and Health Policy, said he has no doubt about the sincerity of President Biden wanting to reduce the burden of cancer in the United States, but he questions whether Moonshot 2.0 outlines the most effective approach.
“By focusing on earlier diagnosis and treatment of cancer, rather than prevention of new cases, Moonshot 2.0 misses key opportunities for reducing the disease burden,” Dr. Freudenberg told Blood Cancers Today.
In early February, Dr. Freudenberg published an opinion piece detailing the shortcomings of the Moonshot 2.0, including its lack of funding and a failure to make prevention a priority.8 “There is a question of whether a significant increase in what we know can come about if there are no dollars assigned,” Dr. Freudenberg said.
When the first Cancer Moonshot initiative launched, Congress passed the 21st Century Cures Act (December 2016), which authorized $1.8 billion in funding over 7 years.2 However, there is currently no newly approved funding specific to Moonshot 2.0.
“Funding will be critical to the success of this initiative,” Dr. Nduom noted.
As part of Moonshot 2.0, President Biden has proposed formation of a new entity: Advanced Research Projects Agency for Health (ARPA-H). The goal of ARPA-H is “to improve the U.S. government’s capabilities to speed research that can improve human health.” Funding for this initiative has been included in appropriation and authorization bills pending in Congress.6
“We are all familiar with the NIH grant process,” Dr. Nduom said. “That process has created a lot of high-impact, important research in our field, but I don’t think any of us are satisfied that it is the only way to get funding to researchers.” According to Dr. Nduom, ARPA-H would be funded with about $6 billion on an annual basis and those funds would be in the hands of a small group of program officers who have the ability to fund research more quickly. “Another less exciting funding piece is continuing to try to increase NIH funding across the board,” Dr. Nduom said. “In the current and previous administrations, NIH funding has been creeping up—when a budget has been able to be passed.”
In addition to the concerns about sufficient funding, Dr. Freudenberg outlined four big opportunities for prevention that the Moonshot 2.0 overlooks. “In my mind, these four opportunities should be the focus of a coordinated federal effort to reduce the burden of cancer,” he said.
The first missed opportunity is reduction of air pollution, which has been linked with hundreds of thousands of lung cancer deaths worldwide each year.9 “Enforcing existing laws and updating air pollution regulatory apparatus for the 21st century should be a top priority,” Dr. Freudenberg emphasized.
Second would be an initiative to improve the population’s diet and nutrition. “There isn’t some magic ingredient or nutrient that prevents cancer, but cancer has been strongly associated with overweight and obesity, and we have seen a doubling or tripling of obesity in the United States in the last several decades,” he said. “Increasing access to healthy affordable food could prevent many of the 80,000 cancer cases attributed to unhealthy diets each year.”
The third area that should be addressed is tobacco control. It is estimated that the previous century’s tobacco control programs and policies prevented almost 800,000 cancer deaths in the United States from 1975 to 2000.10 According to the American Cancer Society, at least 42% of projected new cancers are potentially avoidable, including “19% of cancers caused by smoking and at least 18% that are caused by a combination of excess body weight, drinking alcohol, poor nutrition, and physical inactivity.”1
Finally, Dr. Freudenberg noted that improving access to health care, including access to primary preventive care and cancer screening services, is another a significant opportunity that Moonshot 2.0 fails to address. “This would give people access to nutritional advice, smoking cessation support, or other advice that might allow for prevention or early diagnosis that could avoid deterioration and premature death,” he said. “Twelve states have refused Medicaid expansion, which has been shown to increase access to primary care, particularly for groups most affected by cancer and other diseases.”
Dr. Freudenberg acknowledged, however, that tackling these issues would require a much more robust approach. “It is easier to propose the biomedical approach because it is more likely to have full backing and support of the pharmaceutical and other industries, whereas regulating the petrochemical industry and the food industry and improving access to health care would not have as much corporate support.”
Can It Be Done?
Despite questions about the best approach—and whether funding will support it—cancer specialists are hopeful that a 50% reduction in cancer deaths can be achieved in 25 years.
“With better screening, innovations in treatment, and the full development of what we know about precision medicine, I think that the 50% decrease in cancer mortality is an achievable goal,” said Dr. Alvarnas.
To gain ground on that goal, advances in cancer prevention, screening, and care have to be realized by everyone, he emphasized.
Dr. Nduom, who admitted being an optimist by nature, also thinks the goal is achievable if advances are made across the board. Reductions can be made by going after low-hanging fruit like increasing screening for breast, lung, and colorectal cancers among the underserved and underrepresented, but new advances are needed as well. “If all we are doing are things that we already can do, that won’t get us to the 50% reduction,” Dr. Nduom said. “We wouldn’t have realized the reductions we have today if we had only kept on doing the things we knew about in 2000.”
To get there, access must be improved, disparities addressed, and financial toxicities reduced. Work needs to be done to continue to bring new innovations available at academic centers to community treatment centers. The community must work together to come up with new ideas, particularly to make progress in rare cancers and childhood cancers.
“We have tools federally and within the states to fund health insurance for individuals and to expand health insurance coverage to those not currently earning enough,” Dr. Nduom said. “Having a healthier workforce and populace is something we should all be able to get behind.”
—Leah Lawrence is a freelance health and medical writer based in Delaware.
References
- American Cancer Society. Cancer Facts & Figures 2022. Accessed April 7, 2022. www.cancer.org/
research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2022.html. - National Cancer Institute. Cancer Moonshot. Accessed February 28, 2022. www.cancer.gov/research/key-initiatives/moonshot-cancer-initiative.
- National Cancer Institute. Cancer Moonshot Progress. Accessed February 28, 2022. www.cancer.gov/research/
key-initiatives/moonshot-cancer-initiative/progress. - Liu MC, Oxnard GR, Klein EA, et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020;31(6):745-759.
- The Galleri® Test. Accessed March 2, 2022.
www.galleri.com/the-galleri-test. - The White House. Fact Sheet: President Biden Reignites Cancer Moonshot to End Cancer as We Know It. Updated February 2, 2022. Accessed February 28, 2022. www.whitehouse.gov/briefing-room/statements-releases/2022/02/02/fact-sheet-president-biden-reignites-cancer-moonshot-to-end-cancer-as-we-know-it.
- National Cancer Institute. Cancer Disparities. Accessed March 1, 2022. www.cancer.gov/about-cancer/understanding/disparities.
- Freudenberg N. Cancer moonshot 2.0: a missed opportunity for prevention. Published February 5, 2022. Accessed February 28, 2022. www.statnews.com/2022/02/05/cancer-moonshot-missed-prevention-opportunity.
- Turner MC, Andersen ZJ, Baccarelli A, et al. Outdoor air pollution and cancer: an overview of the current evidence and public health recommendations. CA Cancer J Clin. 2020;70:460-479.
- National Institutes of Health. Nearly 800,000 deaths prevented due to declines in smoking. Published March 14, 2012. Accessed February 28, 2022. www.nih.gov/news-events/news-releases/nearly-800000-deaths-prevented-due-declines-smoking.
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