NCI starts to unpack Biden’s Moonshot 2.0 goal to halve cancer death rates over 25 years

Ned Sharpless: I thought I’d talk a little bit about the past, the NCA 50, briefly on that. A little bit about FY22, which is still very much the current topic of business and then spend the rest of the time talking about the president’s announcement around the new Cancer Moonshot or the supercharged moonshot, as the president called it. 

So, I think when we last met as a whole group in early December, we were still a few weeks out from the actual anniversary of the signing of the National Cancer Act on Dec. 23.

It was a really great, I think, sort of tsunami of interest across the cancer research community around this anniversary. And I think we had great buy-in from everyone interested in cancer research to talk about this anniversary and including a great pickup in the media. 

And we were delighted when the first lady provided this wonderful video in honor of the National Cancer Act’s 50th anniversary, enunciating some of the challenges that remain, but also talking about some of the progress we made. I found that tremendously compelling and really grateful for the White House’s support around that anniversary, particularly the first lady’s really a real friend of cancer research. 

Budget, appropriations, paylines

So, let me briefly say a couple words about ‘22. That’s still a top order of business. As a reminder, I generally try and always show the slide when I speak to the NCAB. You see our allocation for the last couple of years, as well as the president’s budget mark and the house mark for 2022 in light blue to the far right. 

You see the orange bars representing the 21st Century Cures, which funded the original Cancer Moonshot, as well as the $50 million appearing in 2020 for the CCDI, which is now just sort of at the end of a second year, and also the white box there to indicate the one time multiyear funding for coronavirus research that the NCI continues to do.

We are still in a continuing resolution. We have had some members of the Congress talk about the possibility even of a full year, continuing resolution, which would be very problematic for the NCI. We’ve seen maybe a little bit of progress and some optimistic stuff happen in the last few weeks, but lack of having a ‘22 budget, as you can imagine, provides some budgetary challenges and planning challenges for the National Cancer Institute.

The most important, I think, of which is shown, which is that we still operate under these very low interim paylines for 2022. So, ninth percentile is for established investigators and 14th percentile for early stage investigators. And we’re presently funding non-competing awards at 90% during this period of uncertainty. 

We all hope and believe that once a budget is passed, we will be able to improve these interim paylines and particularly improve the funding for non-competing grants. But we’re not out of the woods yet.

I actually had the opportunity to talk to one of the appropriators, Tom Cole, about this at the Cancer Moonshot event. And he told me that he thought they’d get a budget and they’re making progress, but the full year CR is still something we have to worry about. So, stay tuned.

I also want to a point to this op-ed piece in the Scientific American, by [Sens.] Chris Coons (D-DE) and Jerry Moran (R-KS), a bipartisan group of senators who have been strong supporters of American biomedical research, including cancer research. 

And they talk about the kind of support that they think Congress should provide to really help us beat cancer as they call it. And it’s great to hear this kind of bipartisan interest in supporting cancer research at the same time as we’re beginning to discuss what comes next in terms of Cancer Moonshot.

Cancer Moonshot 2.0

So, I think you can clearly see the White House is really interested in ending cancer as we know it, making progress for patients. 

The Congress in a bipartisan manner has shown their willingness over the last several years and their interest in providing support for cancer research and that persists through today. 

And we have a community of researchers and scientists and patient advocates that want to do that too. So, I think the stars are favorably aligned for progress against cancer.

We, as mentioned, last Wednesday [Feb. 2], had this lovely event where President Biden announced his plans to supercharge the Cancer Moonshot and end cancer as we know it. And this was really a big moment for the National Cancer Institute, but I think for cancer research in general and something that we’ve eagerly awaited. The president said that fighting cancer was a top presidential priority and expressed exuberance for the progress of the Cancer Moonshot.

I think it’s important to note the success of the initial Cancer Moonshot launched in 2016 and which has been led so ably at the NCI by Dr. Dinah Singer. And this has been a really large contributing factor to our progress over the past five years. And this is what the president pointed to as enabling this broader and now more ambitious set of goals.

And the event last Wednesday was the kickoff of that. It was step one in which he laid important goals and talked about some of his priorities. I’ve seen first hand the passion and compassion of the Bidens. And this is just such a powerful example of that, of their commitment. 

This really transcends all of government. It’s bigger than any one agency or office. I have complete confidence that President Biden will take the steps necessary to ensure that this aspect of his agenda stays on track, and that’s changing the experience of patients with cancer.

And the president describes this as a really, a whole of government approach. And there’s a great opportunity in that. And you can sort of see in the photograph to the left there several cabinet secretaries. He’s convening a Cancer Cabinet of which the NCI is honored to be part of, to bring together departments and agencies across government to help establish and make progress on the goals of ending cancer as we know it.

This includes 19 agencies such as HHS and the NCI and DOE and DOD, CMS, OSTP, CDC, FDA, EPA, VA, and others. So, an acronym soup there, but really that’s the waterfront of government, all parts of the government that have interest in cancer research and cancer progress. It’s clear that NCI will be primarily responsible for the research aspects of this work, but the administration understands that this is really bigger than just a research question for the National Cancer Institute.

It’s not just about developing new treatments and better prevention, it’s about ensuring access and improving how care is delivered within communities and promoting health equity. I think we’ll see a lot of new ideas come out of this Cancer Cabinet, and I’m really excited for this announcement as well.

I just wanted to remind everyone that we are still very excited about moonshot, the original moonshot or Moonshot 1.0, and that is very much a work in progress where the NCI is very proud of this research. We’re creating these 70 new consortia, more than 70 new consortia and funding more than 240 new research projects working on a wide variety of areas to really accelerate cancer progress in the translational space. 

You can see on the right here, the funding for that initiative sunsets in ‘23, and therefore it’s a great time to be talking about supercharging the moonshot.

We have thought a lot, working with colleagues in the White House, about what it would mean to end cancer as we know it. And if you watched the event, or were there, or read about it afterward, you likely saw how some of these new goals are being presented, a further refinement, really sort of understanding how we know cancer today and how we can work to transform that reality.

And so, a few of these descriptions are shown here to give you a sense of some of the areas that are being envisioned. Not every promising avenue of research is explicitly called out, but I think taken together, this begins to present a picture of the scale and scope of the vision and the directions that are understood to be important and promising.

I might argue this is different from the way we often frame opportunities within the scientific community. So, I think we’re prone to talk about targeting RAS or understanding the tumor microenvironment or elucidating the interplay of multiple transcription factors in a cell. 

And those are worthy goals, and that’s an important way of doing science with the NCI as a long tradition of supporting.

But what we’re really doing here, or what the next phase of the moonshot is doing very intentionally, is looking at what cancer is today and how patients experience it and how we can change what is a tragic diagnosis for many patients that affects their lives day in and day out. And so, these begin to reflect the thinking of the White House and the NCI on this topic, but I think we will have a lot more work to come in these areas.

Reducing age-adjusted cancer mortality

So, one important way to talk about changing the experience of cancer is examining this through the prism of cancer mortality, age-adjusted mortality in the United States.

And I’ve talked about this a lot before, but I think it continues to be a really good metric to think about progress in cancer, because it’s not biased by things like lead-time bias or screening bias and it’s a metric we collect annually and look at very carefully along with the CDC and other agencies. I think it is a great way to talk about what cancer progress might look like. 

You can see here data just from 2005 to 2019, a very striking decline in age-adjusted cancer mortality across the United States. But you can also note that there’s a lot of heterogeneity even persisting today, that there are some states that have high rates of cancer mortality relative to other states that have quite low rates of cancer mortality.

While this progress has been made across the country, that progress is not even. And this begins to make you help one understand the complexity of a metric like cancer mortality, and the challenges of making progress against mortality. I also want to explicitly thank Zaria Tatalovich of DCCPS for helping me organize these data this way.

So, the president and colleagues in OSTP have decided a cancer mortality goal is the right way to think about it. And this was one of the major announcements of the event last week. The president set a goal to reduce the death rate from cancer by at least 50% over the next 25 years.

A reduction of the age-adjusted mortality from the most recent rate of 146 deaths per 100,000 to 73 deaths per 100,000, that would put cancer much lower as a cause of mortality, nationally, and would represent a huge change in the experience of cancer nationally, and would be really a crucial step, I would think, towards any cancer as we know it.

I believe this is a bold goal, but I also commend the president for enunciating such an achievable goal. So, this is not a pie-in-the-sky-we-can’t-do-this kind of thing. I think this is a very achievable step, given that cancer mortality has declined substantially since the 1990s. And we can continue that trend and even accelerate it to meet this goal of the White House.

And as I said, looking back at mortality again, promoting health equity is a big part of ending cancer as we know it. I don’t think the president meant ending cancer as we know it for some people. The president was clear that he wants all Americans to benefit from this progress. And so, one, it has to take a very honest look about the topic of health and inequities in our country as influenced by things like rurality and poverty, and in this case, race and ethnicity.

And so, I share those mortality data, and they were very complicated when you just added in geography for all comers, but then when you further segment it by race and ethnicity, you can see the story gets even further complicated. You’ll notice that non-Hispanic, Black patients have worse outcomes in terms of mortality than all of the groups. Even though there’s an improvement over the years, there’s still significant worsening, significantly increased mortality.

You’ll see this geographic disparity for aggregate data and different populations. The non-Hispanic, American Indian, Native American are not homogeneous. You’ll see that there are stark differences depending on the geography. So, there are some parts of the country where the AIAN data looked pretty good. And then there are other parts where they’re persistently high mortality rates, Kansas, Oklahoma, for example. 

There are a lot of complex reasons to describe this heterogeneity, things like tobacco use. Interestingly on Feb. 5, Navajo Nation enacted the first commercial tobacco ban on American Indian tribal land. So, an important development in terms of cancer control there. 

But to achieve the mortality goals that the president enunciated, we really have to tackle these inequities. We have to make progress for those Americans that have the worst outcomes because of lack of access or structural racism or poverty or wealth or education, or the things that create these cancer health disparities.

Ramping up screening

One of the things the White House has been talking a lot about as a focus of the next Cancer Moonshot is prevention, screening and early detection. These are important tools for controlling cancer at the population health level and tackling some of these equities I mentioned requires closing gaps and screening behaviors, for example.

So, fortunately, the President’s Cancer Panel recently took this topic on and has just released their report, shining a spotlight on cancer screening, and they identified key gaps and barriers and provided recommendations to increase equitable access. 

And here you see Edith Mitchell and John Williams and myself at the moonshot event, who are two of the three members of the President’s Cancer Panel. Early detection can reduce the need for aggressive cancer therapies, sparing side effects that lower quality of life and increase the financial burden.

And their report cites some barriers. It identifies lack of knowledge of guidelines, lack of provider recommendations, fears or concerns about medical procedures, difficulty navigating the health system, logistical challenges, including things like lack of transportation and parking, and lack of access to medical services.

And the report makes some recommendations on how to help all Americans better understand when and how they should be screened and how to improve access to cancer screening through community-oriented outreach and expansion of self sampling to screen for things like cervical cancer and colon cancer. 

It also recommends the healthcare systems and medical offices set up systems and processes that allow all members of the medical team to work together to really support cancer screening and make it a priority. And this is particularly a priority given the last two years of pandemic that we’ve had, that has a dramatic effect on cancer screening.

And here’s one way to look at those data showing the plummet in terms of screening rates that occurred early in the pandemic and really have not recovered. 

And you see the president’s call to action in this area, noting we, over the pandemic period, missed on the order of more than 9 million screenings for cancer. 

And we have to get those back on track for breast cancer, colon cancer, cervical cancer, lung cancer. Cancer screening in some aspects were under utilized prior to the pandemic. And so, not only do we need to recover, but actually increase what we were doing in the pandemic for things like lung cancer screening.

The president called for ensuring that everyone in the U.S. equitably benefits from screening through, at home screening, through mobile screening and communities without access to a clinic, through community health networks, and other important ways to reduce barriers to screening.

And the NCI will work with these designated cancer centers and other networks to make clear that cancer screening is a national priority and a real opportunity to affect cancer mortality at the population level. NCI will also collect qualitative and quantitative data to understand the need and disseminate these data and best practices in partnership with other parts of government like CMS, HRSA, and CDC.

Multi-cancer detection tests

One area of interest across the federal government continues to be the to

pic of multi-cancer detection tests. These are these tests that have the potential to detect many cancers simultaneously in a single blood-based assay in an otherwise healthy individual. And if the tests work to the extent we would hope, we’d have the potential to reduce cancer mortality.

The White House announced that federal agencies led by the NCI will develop a focused program to expeditiously study and evaluate multi-cancer detection tests. But these tests require rigorous testing. And I don’t think we can assume that these things will necessarily work. Screening and early detection has the potential for overdiagnosis and overtreatment and therefore can cause harm.

And so, one step that the NCI has already made is to drop the E. You’ll notice the acronym is usually MCED, M-C-E-D. Doug Lowy has pointed out that the fact that they detect early cancer is not proven. And so, Doug has convinced us all to call it multi-cancer detection tests. And I think he’s right. Also, you notice on the right here, we see an RFI seeking responses through March 21 to help us think about this portfolio. And I know we’ve talked about this topic some before with the NCAB, but it continues to be an area of major interest.

I’ll briefly show a little bit of work that we think could be important in terms of the president’s goals of ending cancer as we know it. So, with regard to prevention, there’s a really interesting study published recently that was co-authored by DCCPS, DCEG, and the CDC, and it really talks about the potential public health benefits of changing daily physical activity.

So, the study used accelerometer measurements to examine association of physical activity and mortality in U.S. adults to estimate the number of deaths prevented by modest increases in activity. 

They use data from the National Health and Nutrition Examination Survey or NHANES of 4,800 adults, 40 to 85 years old. And they found that increased activity was associated with a decrease in the number of deaths per year. One week of monitoring may not reflect changes in activity over time and the study design limits really can’t establish causality.

So, clearly, more research is needed. We think this is an important and potentially actionable result. We believe activity in part affects obesity, which is a growing problem in the United States and has become one of the leading modifiable behaviors in terms of cancer risk.

And therefore, activity plays some role in reducing the population of mortality associated with the obesity-associated cancers. And, importantly, the study shows that small amounts of additional activity can really make a difference.

New studies on TILs

To end cancer as we know it, we also will need to develop new therapeutics. And so there’s a lot going on in this area in cancer research. And I think this is one of the important reasons why we also have such a passion and strong support at the NCI for investigator-initiated basic cancer biology, because that’s what is the substrate for these kinds of new discoveries. But as you see just every week, there’s new exciting ideas in terms of cancer therapy.

And so, Steve Rosenberg, and particularly I, had a pretty good week last week. I had two papers out related to tumor infiltrating lymphocytes from his group. So, the first paper shown on the left was in JCO and was on breast cancer. And while this was patients with refractory breast cancer that had failed multiple prior treatments, it’s still a very important cause of cancer death. 

Steve uses these personalized, tumor-infiltrating lymphocytes to treat these patients with metastatic breast cancer. The results of this were just this phase II trial that happened at the NIH clinical center. Researchers use whole genome sequencing to identify mutations and tumor samples from 42 women. 

You’ll notice the acronym is usually MCED, M-C-E-D. Doug Lowy has pointed out that the fact that they detect early cancer is not proven. And so, Doug has convinced us all to call it multi-cancer detection tests. And I think he’s right.

They isolated TILs from the tumor samples and tested reactivity against neoantigens produced by different mutations that they found in the tumors. And they showed that more than two-thirds of the women, 28 out of 42 with metastatic breast cancer had TILs that recognized at least one neoantigen and generated evidence of an immune reaction.

And so, for six of those women, they were able to reinfuse TILs that they’d grown in the lab and return them to the patient along with treatment with a checkpoint inhibitor to prevent tumor TIL exhaustion, if you will. And the tumor shrunk in three of the six women. 

So, I think it’s a promising set of studies in a highly treated population and shows the power of finding anti-cancer immune cells, even in people who wouldn’t have thought would be good candidates for immuno-oncology. The second paper shown on the right is in science and sort of identified expression profiles of tumor-specific TILs. 

They found these TCR clonotypes from 10 metastatic human tumors and did single-cell transcriptomic analysis. And really, this is important because I think it helps you identify, in the cancer, of those many tumor-infiltrating lymphocytes, those that are capable of inducing sort of anti-tumor response and makes their production and selection much simpler and would be an important step to sort of bring TILs to more general usage.

Right now, this is highly complicated science done in the intramural program at NCI, but if this is going to become scalable in any way, these are really important research questions to address.

New director for childhood cancer

And our efforts to end cancer as we know it must also account for differences in specific populations, both from a health disparities perspective, but also from a population perspective. So, the NCI has long been committed to unraveling the intricacies of childhood cancer, recognizing that children are not just little adults. 

Our efforts in the Childhood Cancer Data Initiative had demonstrated really unique opportunities in this area, but also some significant challenges that remain before us. 

And I felt like I needed more help thinking through with these pediatric cancer issues. And to that end, I’m pleased to announce that Brigitte Widemann will serve as a special advisor to the director for childhood cancer.

Brigitte will join the NCI scientific program leaders and assume a leadership role within the Childhood Cancer Data Initiative and will give a lot of advice to the NCI director. Brigitte is a practicing pediatric oncologist who has collaborated with many experimental institutions and is familiar with NCI’s entire childhood cancer research portfolio. And I think she’ll really bring this valuable clinical and scientific perspectives on research gaps and gaps in treatment. 

She will continue her position as head of the pharmacology and experimental therapeutic section and as chief of NCI’s pediatric oncology branch, but in addition to that, she’ll be giving the NCI director’s office advice. Her pioneering research on neurofibromatosis, NF1 resulted in the first FDA-approved medical therapy for children with NF1. 

That was last year, very exciting development on a congenital cancer predisposition syndrome discovered decades ago by Francis Collins. Her work in this area led to her nomination for a Sammie, for a Service to America’s Award in 2021. And she won several other awards last year.

And Brigitte’s appointment comes at a time of great progress and opportunity in childhood cancer research. So, we’re very excited about having Brigitte’s wisdom to help now.

Zero tolerance for misconduct

I want to be sure to emphasize, especially in light of events earlier this week, that one thing the NCI is about, we are unequivocally committed to ensuring civility, kindness and mutual respect in our workplace. These are core values at the NCI and at the NIH. We believe this is how people do their best work. 

The NCI is not a place where we tolerate bullying and harassment of any kind. NIH policy is very clear and is shown here in a statement released from Larry Tabak earlier today.

Harassment of inappropriate conduct of any kind will not be tolerated. Timely inappropriate action will be taken against any individual found to be in violation of this policy. 

At NCI, we have a workplace civility and anti-harassment program that is coordinated by a workplace civility committee made up of senior representatives across the NCI’s various divisions and centers.

We have communicated and continued to communicate clear policies in this area and have provided toolkits and training and incorporated anti-harassment into our employee onboarding and employee performance evaluations. We also have channels accessible for anyone who experiences harassment to report it safely and discreetly, without fear of retaliation.

We take timely and appropriate actions to respond to all reports, and we take this commitment very seriously. And we believe that doing so is essential to fulfilling our goal, to enable all staff at the NCI to bring their best selves to the research endeavor and reach their full potential and to contribute to our mission, to help reduce cancer’s burden.

Moonshot momentum

I’d like to close with a bit more reflection on recent events. As I have said, I’ve been so impressed by the first lady’s grasp of cancer research and her grace and sincerity when working on this issue. 

At the podium last week, she echoed what I truly believe that we are in this golden age of cancer research. And I think this speaks volumes. 

She and the president are just fired up about the need to make progress in kids’ cancer. They believe the time is now to make that progress and that we will succeed. It’s hard not to be inspired by that. I found this so invigorating and it was so good to galvanize all of us interested in progress for our patients.

Also, at that event, Vice President Harris spoke about her mother’s work as a cancer researcher and her mother’s death due to colon cancer.

And you could really hear, in the vice president’s voice, her respect and love for her mother and her heartfelt passion and commitment to making progress against cancer. She said that this focus on cancer, the Cancer Moonshot demonstrates who we are as a nation. 

And I quote, “In America, we not only dream, we do. We not only see what can be, we see where we want to go in a way that we can reach for the moon and we plant our flag on it.” 

So, that’s a great reminder of the point of the moonshot and why the president and the White House like this metaphor. And it really talks about galvanizing all across federal government for this shared mission to end cancer as we know it.