The future of cancer prevention (part 1)

April 5, 2019 — The statistics on cancer worldwide are staggering:  In 2018, more than 18 million people worldwide were diagnosed with the disease, and nearly 10 million died from it. And the burden of cancer is only expected to grow in the coming decades, thanks to a combination of the world’s aging population, the adoption of unhealthy lifestyles, and environmental exposures linked to cancer.

The challenge of combating cancer may seem daunting, but research has shown that one-half to two-thirds of all cancer cases could be prevented if societies fully implemented currently available cancer-prevention strategies. At the same time, there is also a need to develop new strategies for prevention and screening. That’s why we’re devoting our next two episodes to the future of cancer prevention and diagnosis. In part one you’ll hear from Timothy Rebbeck, director of the recently launched Zhu Family Center for Global Cancer Prevention. During a wide-ranging conversation Rebbeck explained the current landscape of cancer prevention and detection—and outlined his interdisciplinary approach to pushing the field forward.

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New center for cancer prevention launched at Harvard T.H. Chan School of Public Health (Harvard Chan School news)

Full Transcript

NOAH LEAVITT: Coming up on Harvard Chan: This Week in Health…the future of cancer prevention and early detection.

TIMOTHY REBBECK: Most cancers can be cured if they’re diagnosed early, and it’s really clear that if you wait the chances that you’ll survive a cancer diagnosis drop dramatically. So, we feel that it’s important to do as much as we can to have cancers diagnosed as early as possible, or to prevent the cancer from being diagnosed at all through primary prevention activities.

NOAH LEAVITT:  In this week’s episode, we speak with the director of an innovative new research center that wants to change how we think about preventing and diagnosing cancer.

Hello and welcome to Harvard Chan: This Week in Health. I’m Noah Leavitt.

The statistics on cancer worldwide are staggering.

In 2018, more than 18 million people worldwide were diagnosed with the disease, and nearly 10 million died from it.

Roughly 44 million people around the world are living with cancer, and it is now the leading cause of death in many parts of the world.

And the burden of cancer is only expected to grow in the coming decades, thanks to a combination of the world’s aging population, the adoption of unhealthy lifestyles, and environmental exposures linked to cancer.

Low- and middle-income countries are particularly vulnerable.

The challenge may seem daunting, but research has shown that one-half to two-thirds of all cancer cases could be prevented if societies fully implemented currently available cancer-prevention strategies such as vaccinations against infection-related cancers, screenings such as mammography and colonoscopy, personal lifestyle changes, and avoiding exposure to environmental carcinogens.

But there is also a need to develop new strategies for prevention and screening.

And that’s why we’re devoting our next two episodes to this topic.

You’ll be hearing from two scientists affiliated with the Zhu Family Center for Global Cancer Prevention, that was really recently launched here at the Harvard Chan School.

In part one, I’ll be sharing my conversation with Timothy Rebbeck. He’s the Center’s director and Vincent L. Gregory, Jr. Professor of Cancer Prevention at the Harvard Chan School and Dana-Farber Cancer Institute.

During a wide-ranging conversation Rebbeck explained the current landscape of cancer prevention and detection—and outlined his interdisciplinary approach to pushing the field forward.

In part two—our next episode—you’ll hear from Wendy Garrett. She’s on the steering committee of the Center and is professor of immunology and infectious diseases at the Harvard Chan School.

Garrett’s fascinating research focuses on connections between our microbiome and colon cancer.

Garrett and colleagues recently received a 20 million pound grant from Cancer Research UK to seek out ways to manipulate the microbiome to better prevent and treat colorectal cancer.

That’s all coming up in our next episode in a couple weeks, but now let’s jump into my conversation with Timothy Rebbeck.

NOAH LEAVITT: So I do want to start broadly here. When we talk about cancer, how large of a problem is cancer around the world? And is it a problem that’s getting worse now?

TIMOTHY REBBECK: So cancer is very variable in different parts of the world. In Massachusetts, for example, cancer is the leading cause of death in the state. It’s the leading cause of death in many parts of the world.

In other parts of the world, it’s not a leading cause of death. For example in low and middle-income countries like Africa, cancer still lags behind infectious disease. But it’s increasing. So for example now, more people died of cancer in Africa last year than died of malaria.

So malaria used to be a major killer because of changes to the way we deal with malaria. It’s dropped a lot in terms of death. But now cancer is taking over.

So I think that’s the issue that we’re facing in a lot of low and middle-income countries is that infectious disease is being controlled, and chronic disease, like cancer, is growing rapidly. So there’s a lot of variability. But cancer is a huge problem.

NOAH LEAVITT: I think you touched on it there are the variability. But are we also seeing kind of shifts in the demographics of cancer in terms of who is being affected over time?

TIMOTHY REBBECK: Yes, cancer is changing in terms of the patterns of who is affected and why cancers are being diagnosed. In low and middle-income countries, for example, the demographics are changing. People are living longer. People are adapting different lifestyles, less physical activity, different diets. People are, in some places, are smoking more than they used to. And so the associated cancers that are diagnosed end up being– are an increasing problem.

In the United States and other parts of the world, we’re seeing demographic changes in the picture of cancer. So, for example, colorectal cancer is now increasing in young adults, and it’s not clear entirely why that is. In general, colorectal cancer rates– death rates are dropping, but in some groups, they’re rising.

In the United States right now, the lead– the fastest growing cancer in terms of mortality is liver cancer. And that’s a reflection of obesity and factors associated with liver disease. And that’s a very different pattern than liver cancer in places like Asia, where the causative factor is hepatitis B virus. So there are changes in exposures, changes in demographics, and changes in risk factors that make the picture for cancer very complex.

NOAH LEAVITT: And so, I know this new center, the Zhu Family Center for Global Cancer Prevention, it’s primarily focused on two areas, which are prevention and early detection of cancer. So given everything you just kind of laid out with this variability, and, I think, some unanswered questions that you still have, I mean, why is it so important to focus on those areas, prevention and early detection?

TIMOTHY REBBECK: Most cancers can be cured if they are diagnosed early. And it’s really clear that if you wait, if there is a delay in diagnosis or a delay in treatment, the chances that you’ll survive a cancer diagnosis drop dramatically. So we feel that’s important to do as much as we can to have cancers diagnosed as early as possible or to prevent the cancer from being diagnosed at all through primary prevention activities. This will have both social impact, health impact on populations.

There are cost implications by doing cheaper, more effective strategies rather than waiting for very expensive treatment and palliative care strategies. It eliminates and reduces suffering in the population on a lot of different levels. So prevention can really be an important tool, and the early detection can be an important tool in lowering the cancer burden in the population very broadly. And so we feel like an investment in this area is timely and will have benefits on a lot of different levels, social, economic, and in terms of health care.

NOAH LEAVITT: And the statistic you have in your website that research has shown that as many as 2/3 of cancer cases could be prevented if countries implemented proven cancer prevention strategies. So what are some of the strategies? What do we know that works already when it comes to prevention?

TIMOTHY REBBECK: We have a lot of tools that are very effective in preventing cancer. So one is vaccination. In China right now, almost all newborn babies get hepatitis B vaccine. That is going to lower the risk of liver cancer in that population, which is a huge problem in China. HPV is another vaccine that prevents HPV-related cancers like cervical cancer. Cervical cancer has been estimated to be completely eliminateable or could be completely eliminated if everybody received the HPV vaccine on an appropriate timing.

So we have vaccines that clearly work to prevent infection-related cancers. We know that smoking is the leading cause of cancer death in most populations, lung cancer and other related cancers. Elimination of smoking from the population has a huge impact.

We’ve seen this over the past few decades where since the Surgeon General’s Report in the 1960s, and taxes on cigarettes, advertising bans on cigarettes, bans of public smoking, smoking rates have really dropped substantially. And you can see the pattern of lung and other smoking-related cancers has dropped very dramatically as a result. So smoking is certainly something that if we could eliminate it entirely would eliminate the major cause of cancer death currently

There are a lot of lifestyle factors that we believe have an impact on cancer risk and cancer mortality. Certainly obesity is one that is a critical factor in determining risk but also outcomes from cancer. Obesity is a huge problem in the United States and other parts of the world. These things that I’m describing are clearly effective, but they’re not easy to achieve.

We also have early detection and screening strategies. So we know, for example, that colonoscopy to detect colon cancers early is very effective in lowering colon cancer deaths. The rates of colon cancer compliance are relatively low or lower than they should be. But that’s true of HPV vaccination. It’s true of smoking cessation.

So we have many, many effective tools, but we don’t use them very well. We don’t– people are hesitant to use them in some cases, or there are cost barriers or access barriers. And we have not innovated the way we use these tools or the way the tools are implemented in a long time, so there’s a lot of opportunity to make things better.

NOAH LEAVITT: And you touched on barriers there. And I imagine the barriers are different versus vaccination versus something like combating obesity, which has all sorts of competing factors. So what would– I mean, I guess when you look at the barriers, what are some of the biggest barriers to implementing these prevention strategies? And are there any kind of ideas about how to maybe try to combat some of these, maybe with an HPV vaccine update, things like that?

TIMOTHY REBBECK: Well, you’re exactly right, that the barriers are substantial and very different depending on what the intervention is. So for HPV vaccination, it’s very clearly efficacious, but there have been concerns from the anti-vac community about the dangers of vaccination in general. And there have been erroneous reports or thoughts that HPV vaccination leads to promiscuity, leads to sexual behaviors that are unfavorable. And parents are worried about that. We know there’s a lot of data that suggests none of that’s true. But people’s beliefs are huge barriers in terms of achieving the rates of cancer prevention in terms of vaccines that we should be able to achieve.

So one of the key areas, key barriers is education, really getting people to understand the truth about the risks and the benefits of some cancer prevention strategies, and to make sure that the knowledge is appropriately transmitted, and myths and other kinds of beliefs that are untrue or unfounded are set aside. And that’s, [? of ?] [? course, ?] a very difficult thing to do.

Smoking is a very difficult thing to eliminate because people are addicted to smoking, and that there are social and economic business pressures that keep people smoking. And it’s very difficult for people– some people to stop smoking because they’re addicted to something. And you could make the same argument about alcohol, which is a cancer risk factor.

It’s very hard to get people to change their lifestyle. Exercise has been clearly shown to have beneficial effects in lots and lots of different ways. But getting people to exercise effectively is not easy. So there are lots of different barriers.

Some of the barriers are medical. Access to care, so for colonoscopy screening, there are people that just don’t like the idea of colonoscopy screening. The preparation may be difficult.

And so there are access barriers to people wanting to– or not wanting to have a certain procedure, and then their ability to get into a medical community or a health care setting to actually make it happen. So there’s a series of barriers, and they’re all different depending on the kind of intervention, the kind of preventive strategy. But the implementation science around getting people to do this is a critical aspect of how we’re going to make preventive strategies better in the population.

NOAH LEAVITT: And you talked a few minutes ago about early detection tools and this need for new tools. So where is the field of early detection heading? I mean, what’s happening there that particularly excites you?

TIMOTHY REBBECK: There are two areas that are ripe for development in early detection. One is that we have an incredible amount of knowledge of biology of cancer and the underlying mechanism of cancer. And so we can build on that knowledge by understanding what the molecular changes occur early in the development of cancer, what kinds of tissue changes, what kinds of biochemical changes, things that happen in the blood, things that happen that are easily measurable. This knowledge of biology is so good at this point we can really build on that to better understand biomarkers and measures of risk that I think that we haven’t made a lot of progress in using that knowledge for early detection, but we’re right on the cusp of doing that.

And the second thing is technology. We have all kinds of great technologies, including liquid biopsies, the ability to take a blood sample and use it to identify biomarkers or other changes very early on. And these are things that could be done easily, non-invasively, or relatively non-invasively. I mean, now we have the ability to measure blood sugar off a smartphone. So these are point-of-care or home-based kinds of tools that would break down some of the barriers to access in cancer screening.

We also have digital technologies using mobile phones for education, for reminders, for a lot of different purposes. So the combination of having a lot of knowledge of biology and mechanism of cancer, understanding how cancers arise, and the technologies that often haven’t been applied in a early detection setting really are very exciting opportunities that should be built on in the near future to improve strategies for early detection.

NOAH LEAVITT: I think what’s interesting as I hear you talk is that, on one hand, new technology is critically important, but it seems like, I mean, new technology can’t do everything. It can’t solve it. But there’s still this balance of lifestyle factors. So how is someone who’s leading a center focus on prevention, early detection, how do you balance that as someone leading the center of technology versus maybe looking at some of the other important factors?

TIMOTHY REBBECK: For our center, I think it’s really important that we identify a niche that we can make a contribution in. There are lots of groups who are working in prevention and early detection, many of whom have done incredibly important things and are making contributions that we value a great deal. Our question is, what can we do that is not filled alrea– niche that’s not already filled that we can make a unique contribution in? And so, again, the notion of building on the very strong biology, basic mechanistic work that goes on at Harvard and around Boston and the technologies that we have in Boston, is a niche or an opportunity that haven’t been filled in a lot of places up till now. We also have people who are very good at implementation science or putting things into populations.

So I think that the goal over the next year is for us to figure out where we can have our biggest impact around areas that are novel, have not been attempted, or have been successfully achieved by other groups so that we can make headways in new areas. So our philosophy is going to be one of a fairly high risk but high reward because we’re not going to try to do the same old, same old– not that the same old, same old is bad because it’s been very successful. But we’re going to try to do something new and different probably around using the knowledge, and mechanism, and biology, and technology that have not yet been exploited to really impact on prevention, early detection to date.

NOAH LEAVITT: And it seems like this is such an area that’s kind of ripe for collaboration with people from different kind of experiences. So as your role as the center director, how– what do you want to do to foster that collaboration? What are your ideas in that, to bring people maybe who are experts in biology, with people who are experts in implementation science, together?

TIMOTHY REBBECK: So one of the challenges in bringing people together is that people often speak different languages, they come from different backgrounds or academic cultures. And they may appreciate the need for other groups to come into the conversation, but they’re not sure how to do that. They’re not necessarily sure how to have that conversation.

In fact, we often see when we bring people from different disciplines, that they’re saying the same thing, but they’re using very different language. They value different things like where they publish, or what constitutes good science, or what constitutes a meaningful end point to the work. In fact, they’re probably thinking in the similar terms, but the way they approach these problems is quite different. And so part of the goal of the center in bringing interdisciplinary and multidisciplinary groups together is to provide a common language for us to talk about problems and to think about the way that our discipline can bring something by understanding what the other people are doing, how it links to what I’m doing, et cetera.

And there’s a great quote from Karl Popper, the philosopher, who said, we are not students of some discipline, we’re students have problems. And problems can cut across many disciplines. But figuring out how to address a single problem that many of us all care about but are coming out from different angles is the challenge of our center, but exactly what we’re trying to do to bring everybody together.

NOAH LEAVITT: Is there a problem, whether it’s in cancer or, I guess, anywhere else in medicine that’s been solved by that approach that you draw inspiration from?

TIMOTHY REBBECK: There are a number of examples where essentially a new discipline has been developed out of the need to address a particular problem. So I think in recent times the bioinformatics, biomedical informatics world has really blossomed into a field, the data science field. And partly this sprung out of the need for dealing with large amounts of data because the data that we had available in the past, 50 years ago, you could do on– you could do the analysis on paper, or in a little spreadsheet, or a calculator. Now we need a completely different way of thinking about data because it’s just too much to think about as a data point.

And so that discipline has grown into a whole way of thinking about data and problems around genomics, and health data, public health data, large administrative databases. And so brand new methods have been built around the thinking– different ways of thinking about dealing with large data sets. So there is an example where a problem of large data, high-dimensional data was addressed by brand new methods in the new way of thinking. Similarly, we hope to create something that will be a brand new way of thinking about the cancer prevention problem that builds on existing disciplines, and methods, and things like that, but may not necessarily be the same as what we’ve had before.

NOAH LEAVITT: So at your recent symposium that launched the center, [? Sanjiv ?] [? Canberra ?] of Stanford made this point that I was interesting, that while early detection is critical to cancer survival, much of the health care industry’s efforts are targeted at the later stages of cancer. So what can be done, I think, to shift that focus toward early cancer prevention and detection, especially from broader health care industry’s perspective?

TIMOTHY REBBECK: Yeah, that’s a huge problem because most of the biomedical, biotech, pharma industry has been focused around therapeutics. And therapeutics are hard, even [? amongst ?] themselves to find a drug, to develop a drug, to have it approved, and to have it be successful. And so at least at the end of the therapeutic pipeline, there’s something that can be sold, there’s something that could be marketed. The companies that need to make these huge investments can win back some of the investment they’ve made and have an impact.

The problem in cancer prevention and early detection is that a success in prevention, for example, is that you will develop something similar, you’ll develop a drug, you’ll develop an intervention. And you have to apply it perhaps long term, you have to– the people have to comply with it. It might take a huge amount of time and large studies to bring it up to speed where it can be actually– the data, the evidence are there to use it.

But the end is that nothing really happens, right? So that a success in cancer prevention is you do something fairly intense over 20 years and nothing happens. You don’t get cancer.

So that’s a hard endpoint to sell to people, to drug company, to pharma because it’s not like at the end of this you can be able to say you’re going to sell something to somebody. The public health benefit may be clear, but the individual benefit, the medical benefit, is unclear, or it’s not easy to quantify for an individual. So I think the issue there is going to be how we incentivize companies, and people, and health care systems to recognize the value of seeing nothing happen in 20 years, no cancer develop or something like that.

One way to do that is to align the incentives to the individual with the risks and benefits. So an individual, if they recognize that they’re at risk, might be more incentivized to want to do something. If the health care system realizes that down the road if they don’t do something, the costs will be higher, if companies can understand that they’ll make a profit in some way– because that’s what companies are about– those kinds of activities need to happen.

Not easy to achieve. And it hasn’t been something that the cancer prevention world has been very good at, least in terms of companies, and profit, and thinking about how companies, and pharma, and groups like that might want to invest in these kinds of activities. It’s been very difficult.

NOAH LEAVITT: Do you feel like you have a potentially interesting or different perspective on this because, on one hand, you work at Dana-Farber Cancer Institute, but you’re also in a school of public health. So I feel like you have an interesting perspective because you are coming at this from both sides.

TIMOTHY REBBECK: Yeah, absolutely. And this goes back to the notion of being interdisciplinary and thinking across fields. My whole life has been spent being between epidemiology, and genetics, and cancer, and different disciplines that are really quite different from one another. Not everybody has done that, and not everybody has the same motivations to want to do that.

So again, in our center, I think it’s going to be our task to get people to care about some of these interdisciplinary questions and to bring in pharma and industry. So we are already linking to people in industry to talk with them about why they have been unable to, or are not interested in, or whatever to develop some of the things, the successes they’ve had in therapeutics, for example. And I think we have some sense why that is, but I think we’re going to spend a lot of time building these relationships. And by being somebody who comes from– used to talking to people from different areas in academia, industry, et cetera, and government, and policymakers, and things like that, it will be more natural for me and for others who think this way to have those conversations we hope.

NOAH LEAVITT: I know the center is still so new. I mean, you just launched a month ago. But as you look– as you look at in the first couple of years, are there specific projects on the horizon, or people that you might be looking to collaborate with that have you particularly excited?

TIMOTHY REBBECK: Well, very many, there’s– on a couple levels. One is that we’ve already created a network called One Boston for Cancer Prevention and Early Detection. We’re bringing together all of the academic, and health care, and research institutions around the city of Boston, which includes Harvard, and MIT, and Boston University, and Tufts, and the Broad Institute, and others. The notion there is that there’s a lot of strength already built in basic biology, and the clinical care, and technology, and we don’t talk to each other very much.

So we’ve already started having group meetings where we’re bringing together people really from not only different academic disciplines, but in different institutions, people from engineering, and from clinical oncology, and from epidemiology. So that’s been very exciting just to see people in the same room talking about some of the issues, again, the same problem being addressed from very, very different perspectives, but really common, common goals. So that’s certainly one thing that’s very exciting.

We’ve also started to think about how– one of the very important principles of our center is how our work that can impact all populations. What often happens when you develop new technologies or new approaches is that some people benefit from them. Some people, usually wealthy, people with access, or educated people benefit. What happens, of course, as a result is that disparities arise. People without access, who are less educated, have less socioeconomic means don’t benefit from these new technologies.

So one of the things that we’ve been spending a lot of time talking about is how to make sure that anything we develop, anything that we create out of this center can be implemented or designed so that it will be able to be put into federally-qualified health centers, or community health centers, or “in the population,” particularly underserved populations. And by starting to think about what kinds of implementation strategies or prevention strategies we are developing, but thinking about “the population” from the start, we hope will have a bigger impact on all people. And when we say that, we mean different neighborhoods in Boston. But also if we develop something, can it be as readily implemented in Zimbabwe, as in China, as in Chicago, and to think about that early on so that the technologies don’t just benefit the rich.

And so that’s something I think is very exciting. It’s a big challenge. But at least if our impact can be more universal than many of the technologies that have been developed in the past, I think we’ll have a– we’ll make a bigger hit on the cancer burden worldwide.