Shooting for the Moon: Is the Cancer Moonshot a Long Shot?

More than 50 years after President Kennedy declared the United States’ intent to go to the moon – “not because [it is] easy, but because [it is] hard” – President Obama announced the country’s next target. This time, the finish line isn’t an unexplored lunar surface; it’s the “elimination of cancer as we know it,” and reaching this final frontier will require the same kind of dedication and innovation needed half a century ago.1

The National Cancer Moonshot Initiative, which President Obama announced during his State of the Union address earlier this year, is a $1 billion program with lofty goals. “The Initiative aims to bring about a decade’s worth of advances in five years, making more therapies available to more patients, while also improving our ability to prevent cancer and detect it at an early stage,” according to the White House’s fact sheet on the program.

The first steps in achieving these goals are to accelerate cancer research efforts, break down barriers to progress by enhancing data access, and foster collaboration among researchers, patients, public institutions, and private companies. Special attention will be paid to cancer prevention, genomic analyses, pediatric cancer, and developing and optimizing immunotherapy, which has already shown to be an effective treatment in lymphoma and leukemia.

But, while the overarching goals of the Initiative are broad, the initial recommendations are expected to be carefully targeted at the areas that have the most potential to make significant advances in cancer research and care, according to Dinah Singer, PhD, acting deputy director of the National Cancer Institute (NCI).

“We are looking for ideas or recommendations that are aspirational, but feasible,” Dr. Singer told ASH Clinical News. “We can’t be starting something wholly ab initio; it has to be something that we know will have huge potential to help cancer patients.”

It’s an exciting endeavor that could lead to promising advances in the field of oncology and malignant hematology; however, the work to determine exactly where the project’s funding will be distributed and which efforts will be supported has only just begun.

“This is an unprecedented opportunity to make science count for patients, but we do need to make sure that we have realistic goals and expectations for researchers, caregivers, and patients alike,” said Kenneth Anderson, MD, president-elect of ASH and the Kraft Family professor of medicine at the Dana-Farber Cancer Institute and Harvard Medical Center in Boston, Massachusetts.

Liftoff

Shortly after the State of the Union Address, President Obama issued an official memorandum outlining the goals of the Moonshot Initiative and establishing a White House Cancer Moonshot Task Force, led by Vice President Joe Biden, charged with producing a detailed set of recommendations on how to:

  • accelerate the understanding of cancer, including its prevention, detection, treatment, and cure
  • improve patient access and care
  • support greater access to research and data
  • encourage development of cancer treatments
  • identify and address unnecessary regulatory barriers
  • ensure optimal investment of federal resources
  • identify opportunities for collaboration between public and private entities2

Vice President Biden named Greg Simon as the executive director of the Cancer Moonshot Initiative. Mr. Simon was diagnosed with chronic lymphocytic leukemia in 2014, and was the founding president of FasterCures, a non-profit organization with the goal of speeding up the translation between basic research and critical medicines.

The Initiative also established an advisory Blue Ribbon Panel to inform the scientific direction and goals of the National Cancer Moonshot Initiative and report back to the Task Force about the research areas with the greatest potential to drive significant advancement.3

“For example, immunotherapy is likely to be one of the areas that we will want to put a lot of attention into,” Dr. Singer, who is one of three co-chairs of the panel, said. “We know that some immunotherapies, including antibody-based immunotherapies and checkpoint inhibitors, are very promising, but we have a long way to go in understanding when and in which populations they are effective.”

While the Blue Ribbon Panel will be charged with addressing the cancer research issues of the Initiative, the Task Force will address the broader, non–research-based questions of the Initiative.

Formed in April, the Blue Ribbon Panel includes scientific experts from a variety of backgrounds, cancer leaders, and patient advocates. For instance, Deborah K. Mayer, PhD, RN, a professor at the school of nursing and director of cancer survivorship at the UNC Lineberger Comprehensive Care Center in Chapel Hill, North Carolina, brings 40 years of experience as an oncology nurse to the panel, which she said has given her a unique understanding of what it’s like to be on the front lines of cancer care.

“All of the clinicians on this panel have an in-depth knowledge about what patients and families go through,” Dr. Mayer said. “We are also looking beyond treatment-focused groups and toward survivorship and palliative care.”

The panel will have until late August to develop its recommendations before reporting its conclusions to the Task Force and the National Cancer Advisory Board.

To help the panel achieve its task, it has formed a series of workgroups, each comprised of just over a dozen subject matter experts, NCI staff members, and representatives from the private sector and advocacy groups. The panel created seven distinct workgroups; each one is responsible for a different aspect of cancer research:

  • Cancer immunology and prevention
  • Precision, prevention, and early detection
  • Tumor evolution and progression
  • Expanding clinical trials
  • Pediatric cancer
  • Enhanced data sharing
  • Implementation sciences

Each workgroup will create two to three recommendations within its subject area and present ideas to the Blue Ribbon Panel in mid-June. “The Blue Ribbon Panel will then look at all those recommendations, synthesize them, refine them, and ultimately put them into its report,” Dr. Singer explained.

The panel plans to include just five to 10 recommendations in its report to the Task Force and National Cancer Advisory Board. “To truly galvanize people around an idea, to gather the resources we’ll need, and to develop the technology we’ll require, we have to focus on a few things,” Dr. Singer said.

Dr. Mayer added that she believes the Initiative will help address one of the biggest challenges facing cancer research: making sure all people have access to the latest research and treatments. “Our goal is really to see what we can invest in to accelerate research even further, and then to ensure that what we find is available to those in need,” she said.

The Initiative is also answering questions about how the research community can improve clinical trials – especially in adults with cancer, who are less likely to be enrolled in clinical trials than their pediatric counterparts. “How much can we accelerate research if we were able to enroll many more adults in our studies?” Dr. Mayer asked. “How do we take advantage of the data that exist in electronic health records or databases in a way that will help us answer questions outside of clinical trials?”

Follow the Funding

While it’s still unclear how the $1 billion allocated for the Initiative will be distributed, the White House has said the funding will go to support cutting-edge research opportunities in areas such as:

  • Prevention and cancer vaccine development
  • Early cancer detection
  • Cancer immunotherapy and combination therapy
  • Genomic analysis of tumor and surrounding cells
  • Enhanced data sharing
  • Pediatric cancer

The U.S. Food and Drug Administration (FDA) will also receive funding to establish a virtual Oncology Center of Excellence, that will, as the White House stated, “leverage the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics, and devices” to speed the development of new oncology therapies, combination products, and diagnostic tests.

Few details are known about the center’s design, but FDA Commissioner Robert Califf, MD, suggested that reorganizing the agency’s oncology division could help expedite approvals. For example, combination product reviews can be slow because they require approval from the agency’s device and drug divisions; pairing the relevant drug and device review staff together would hopefully alleviate delays.

Addressing a meeting of the Alliance for a Stronger FDA, Dr. Califf said, “It’s not going to be purely virtual.”4

In the fiscal year 2016, the National Institutes of Health has been given $195 million for new cancer activities as part of the Moonshot Initiative, and the bulk of the funding will be included as part of the fiscal year 2017 budget. The Moonshot funding is in addition to the normal funding appropriations for cancer research and care; for instance, the NCI will still have its normal appropriations budget of $5 billion. The Departments of Defense and the Veterans Affairs are also expected to increase their research investment as part of the Initiative.

Ideally, the additional funding will give researchers incentive to study hard-to-treat, more uncommon cancers – those that historically have received a smaller portion of the NIH’s budget than more common cancers.5 The NIH’s funding has ebbed and flowed in the past, and, subsequently, so has the grant funding available to cancer researchers – making them more likely to focus on areas they know can yield publishable results to increase their odds of getting funded.

Only 16 percent of all grant applications are successfully funded, NIH Director Francis Collins, MD, PhD, noted at this year’s Milken Institute Global Conference. “We’re not lacking for ideas, we’re not lacking for talent. We’re scaring away some of the talent.”6

”We will continue to invest broadly in cancer research through our normal mechanisms of investigator-initiated research, our consortia network, and our clinical trials,” Dr. Singer said, “but this Initiative is an exceptional opportunity to do something really different that moves specific fields forward and makes a difference for patients.”

Homing in on the Target

The scope of the Initiative may seem overwhelming, but the sources who spoke with ASH Clinical News said that, as recommendations from the workgroups and the Blue Ribbon Panel come in, its focus will start to narrow and the steps to achieving these goals will become clearer.

Dr. Singer also acknowledged that the Initiative won’t touch on all aspects of cancer research and care. “This is not going to be business as usual. We are looking for things that are exceptional.”

Regardless of which research areas and recommendations are selected as priorities, the announcement of the Moonshot Initiative has created a sense of enthusiasm and camaraderie among researchers.

“There is huge excitement about the possibilities,” Dr. Singer said. “I think people are going to be energized by the amount of attention that is being given to cancer research, even if their own specific area isn’t identified as one that’s ripe for funding.”

The Blue Ribbon Panel hopes that enthusiasm extends to the American public. In addition to including voices from patient advocacy groups on its panel, they are also asking for the public’s input through the Cancer Research Ideas website (cancerresearchideas.cancer.gov). People are encouraged to submit their ideas for research in the areas mentioned above; from this information, NCI hopes to learn more about which issues matter most to the public and which areas the public views as those with the greatest needs and opportunities.

ASH has weighed in on the initiative as well, meeting with the White House in late April to offer its help and support. (See the SIDEBAR for more on this visit.) “ASH is poised to, on one hand, ensure that patients with hematologic malignancies are also benefitting from this Initiative in each of the selected topic areas and, on the other hand, to help assure that we do have realistic goals in each of these areas,” Dr. Anderson said. “We view this opportunity as a jumping-off point for a larger collaborative effort.”

Breaking Down Data Silos

Another hallmark of the Moonshot Initiative is its commitment to data sharing. While this has proven to be a divisive issue among the research community (see last month’s feature story, “Attack of the Data Suckers!” for some perspective), those involved with the effort hope the emphasis on opening up data access will break down barriers between research institutions and enhance the collective knowledge of the research community.

Vice President Biden underscored the importance of collaboration in an address presented at the American Association of Cancer Research’s 2016 Annual Meeting in April.7 “I ask you a rhetorical question: Are we collaborating enough? What can you do? What can we do?”

“The way the system now is set up, researchers are not incentivized to share their data,” he remarked. “Together we can redesign a new system – or adjust to a new system that better supports your efforts and save lives sooner than otherwise would have been. … We have to work together. We have to give you the ability to take chances. We have to help you do what you want to do: Put patients first.”

Improved data sharing will be particularly relevant to those who treat patients with hematologic malignancies, due to the complexity and heterogeneity of cancer. “A genomically profiled, clinically annotated database is essential for to improve the understanding and treatment of hematologic cancers,” Dr. Anderson commented.

He added that, for real progress to take place, institutions, researchers, and private and public entities must collaborate. “The complexity of our diseases requires that we pool data to have significant numbers of patients to reach conclusions and, ultimately, to deliver optimal treatments to our patients. We can learn from our solid tumor colleagues and they, in turn, can learn from us.”

Dr. Singer said that determining the best way to share data is a challenging problem in cancer today, particularly due to the large datasets clinical trials are generating. “To truly learn from these data, they need to be complemented by patient annotation.”

“That’s why the Moonshot Initiative is so important,” Dr. Anderson added. “Hopefully, the Vice President is setting an example that will inspire people to work in partnership on a scale that we simply haven’t seen previously.”

The Promise of Immunotherapy

The Moonshot Initiative seems to be marked by its macro- and micro-level views of cancer. “On the one hand, the Moonshot Initiative is exploring big data initiatives to define the heterogeneity of disease, but, just as importantly, it is also exploring personalized immunotherapies – the most promising area in cancer management today,” Dr. Anderson said. “It’s a very exciting time.”

The Moonshot Initiative will take a deep dive into immune system–based therapies, which have shown success in melanoma, leukemia, and lymphoma. According to the White House, “this approach is ripe for further exploration in a wider range of cancers.”

“The immune system is selective, potent, and very adaptable,” Dr. Anderson explained. “It may be able to overcome the evolution and changes in cancer cells that ultimately lead to resistance and relapse of disease.”

As part of the Moonshot Initiative, researchers are also developing vaccines that could prevent cancer from ever developing or that induce an immune response earlier in the disease course – based on the success of vaccines for cervical cancer and other cancers caused by human papillomavirus. According to the White House, funding will go toward “speeding the development, evaluation, and optimization of safe cancer vaccines targeting unique features of individual cancers.”

“The concept is that these approaches vary and have unique mechanisms of action, but the future promise lies in combining these therapies,” Dr. Anderson said. If researchers are able to achieve a memory immune response against a patient’s own cancer through combination therapies, someday it may be possible that a patient never develops active cancer, he explained.

Targeting the Genome

Although the Moonshot Initiative is still taking shape, the National Institutes of Health (NIH) and the White House have already announced progress in increasing our understanding of the genetic changes that occur within the cancer cell. The NIH is leading the Precision Medicine Initiative (PMI), a research effort to use genomics and big data analytics to develop personalized treatments for many diseases, including cancers. The largest component of this Initiative is the PMI Cohort Program, a long-term health study that will examine genetics, lifestyle factors, and health in an effort to propel precision medicine and identify cancer cures.

In February, the program began accepting volunteers. The NIH wants to enroll the first cohort of 79,000 participants into the precision medicine database by the end of 2016, with a projected total enrollment of 1 million participants by 2019. To spur enrollment, the NIH provided funding to Vanderbilt University in Nashville, Tennessee, to perform a pilot study of direct recruitment initiatives, including a participant website and phone line.8

The NIH also pledged to work with federally funded community health centers to encourage cohort volunteers from underserved populations. “For most of history, medicine has been based on trying to identify what works for the average person,” NIH Director Dr. Collins said in a press conference discussing the program. “We’re all different. This one-size-fits-all approach is far from optimal.” The goal of the PMI Cohort Program and recruitment initiatives is to “empower any person, anywhere in the United States, to raise their hand and volunteer to participate.”

“The PMI focuses on implementing what we have already learned about cancer genomics to clinical trials,” Dr. Singer added. “The PMI and the Blue Ribbon Panel share complementary agendas and, hopefully, both efforts would be moved under a common umbrella down the line.”

Looking to the Future

The White House has set forth a bold goal – eliminating an indiscriminant disease that is estimated to kill 600,000 Americans this year.1 So, with what we know about the Initiative so far, will the moonshot lead to more hits or misses?

“What the NCI has learned in the last decade is that cancer is diverse and is driven by mutations that continue to accumulate as cancer grows,” Dr. Singer said. Some of the mutations are common to many cancers, but others are unique. In other words, one size does not fit all.

While strategies that target the immune system may be more universally applicable and certain approaches target commonalities found within multiple forms of cancers, individual treatment strategies will still be necessary to effectively treat each type of cancer, she added. “We are going to have a lot of different approaches, but the more we learn, the more we can develop those targeted therapies.”

“The solutions are not going to be simple,” Dr. Anderson said. “We will likely look to targeted therapies in combination with immunotherapeutic approaches administered early in the disease course – when the potential for the treatment’s effect is greatest.”

There are still many questions about the future of the Moonshot Initiative – which priorities will be identified and adopted, for one – but those involved in the process say the hematology/oncology community won’t have to wait long before more specifics are known.

A clearer picture will start to emerge by this fall, when the Blue Ribbon Panel will present its top priorities and recommendations to the Task Force and National Cancer Advisory Board. The Task Force is expected to deliver its full report, including the top research priorities, to President Obama in December.

“This is moving fast,” Dr. Mayer said. “I think we have a very strong panel bringing different aspects of cancer and cancer care to the table, but we all recognize our charge is really to look at the whole picture.”—By Jill Sederstrom 


References

  1. The White House. Fact Sheet: Investing in the National Cancer Moonshot. Accessed May 4, 2016 from https://www.whitehouse.gov/the-press-office/2016/02/01/fact-sheet-investing-national-cancer-moonshot.
  2. The White House. Memorandum: White House Cancer Moonshot Task Force. Accessed May 4, 2016 from https://www.whitehouse.gov/the-press-office/2016/01/28/memorandum-white-house-cancer-moonshot-task-force.
  3. National Cancer Institute. Blue Ribbon Panel announced to help guide Vice President Biden’s National Cancer Moonshot Initiative. Accessed May 4, 2016 from http://www.cancer.gov/news-events/press-releases/2016/blue-ribbon-panel-announced.
  4. Friends of Cancer Research. “Pink Sheet – FDA Oncology Center of Excellence Coming, Moonshot or Not.” Accessed May 5, 2016 from http://www.focr.org/news/pink-sheet-fda-oncology-center-excellence-coming-moonshot-or-not.
  5. Carter AJR, Nguyen CN. A comparison of cancer burden and research spending reveals discrepancies in the distribution of research funding. BMC Public Health. 2012;12:526.
  6. “Sustaining the New ‘Golden Age’ of Medical Research.” Panel discussion at the Milken Institute Global Conference, May 2, 2016; Los Angeles, California.
  7. “Highlights 2016: Vision for the Future.” Plenary session at the American Association of Cancer Research Annual Meeting. April 20, 2016; New Orleans, Louisiana.
  8. National Institutes of Health. “Preparing to Launch the Precision Medicine Initiative Cohort Program.” Accessed May 6, 2016 from https://www.nih.gov/about-nih/who-we-are/nih-director/statements/preparing-launch-precision-medicine-initiative-cohort-program.

ASH Offers Expertise to Help With Initiative

Leaders of the Cancer Moonshot Initiative are asking for public comments, and ASH has made sure hematology’s priorities have been heard. In April, ASH representatives met with Executive Director Greg Simon at the White House to share ASH’s scientific recommendations for the Initiative.

“Hematologists are pioneers in several fields that are revolutionizing cancer research, including immunotherapy, cell therapy, and genome sequencing – areas of study that are now showing great promise in treating solid tumors in addition to blood cancers,” ASH President Charles S. Abrams, MD, said in a statement supporting the Initiative.

Commenting on the meeting, Kenneth Anderson, MD, said that ASH was well received. “Mr. Simon could not have been nicer and more receptive and spent several hours with us and appreciated the value that ASH can bring to the Moonshot effort.”

Prior to the meeting, an ASH task force on precision medicine was charged with creating a series of recommended action items for the Moonshot Initiative.

For a full list of ASH’s recommendations, visit www.hematology.org/Research/Recommendations/Moonshot-Initiative.

Sidebar photo
Pictured L to R: Suzanne Leous, ASH staff; Kenneth Anderson, MD, president-elect of ASH; Greg Simon, executive director of the Cancer Moonshot Initiative; Martin Tallman, MD, and Tracy Roades, ASH staff.

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