A Field in Motion: Fighting Cancer with Exercise

Exercise scientist Lee Jones studies the ability of exercise to limit the cardiovascular side effects of cancer therapies and investigates whether exercise can help treat cancer, prevent recurrence, and even improve the effectiveness of conventional treatments.

Memorial Sloan Kettering Exercise scientist Lee Jones
Exercise scientist Lee Jones

As his title suggests, exercise scientist Lee Jones studies the effects of physical activity with scientific rigor. He’s currently the Director of the multidisciplinary Cardio-Oncology Research Program (CORP) at Memorial Sloan Kettering, which works to improve the health and longevity of people with or at high risk of cancer. Using an approach that spans basic and clinical science, the group is designing and testing the impact of structured exercise training programs on preventing or mitigating the cardiovascular side effects of cancer therapy as well as determining whether exercise is an effective treatment for cancer itself. Here, he talks about some of this work.

Can you tell us a little about the history of the relationship between exercise and disease?

If you look at the role of exercise in other chronic, noncancer diseases such as heart disease, heart failure, and type 2 diabetes, it’s typically part of the standard of care. It’s actually the central piece of treatment for a lot of these diseases. So for example, somebody who’s had a heart attack is referred to cardiac rehabilitation as a standard of care, in which exercise therapy is the primary component and everything else is built around it.

An exercise prescription is also one of the frontline therapies for the prevention of many diseases. If you go to your primary care physician and you’re at risk for certain diseases, one of the first things he or she will talk to you about are lifestyle interventions, whether that's stopping smoking, modifying your diet, or losing weight — and the conversation always, or should always, include regular exercise. In cancer, there is convincing evidence that regular exercise is associated with a significant reduction in the risk of certain forms of the disease such as breast, colon, and prostate.

So what do we know — and not know — about the role of exercise in cancer?

While we’ve recognized the critical importance of exercise therapy for other diseases since ancient times, the value of exercise in people with cancer was left largely untouched until recently. The prevailing view was that cancer is associated with poor outcomes and patients who either are undergoing or have finished intensive cancer treatments would not be able to tolerate participating in structured exercise programs. Because of this, many patients are still being advised to rest and avoid strenuous activities.

However, things are now changing radically. There are a number of reasons for this. Perhaps the most important is the enormous progress we’ve made in cancer screening and prevention as well as in treatment. In combination, this now means that individuals are living longer with cancer than ever before, and accordingly, certain cancer diagnoses are no longer considered a death sentence. Indeed, today there are nearly 14 million people in the United States living with a history of cancer. Therefore, exercise has gained a lot of traction as part of the survivorship movement, and vice versa — survivorship has gained in importance because of the work that has come out of exercise.

Can you talk in a general sense about the type of work you and your research team are engaged in?

In the CORP, we are essentially focused on two fundamental things.

The first is whether we can better mitigate the immediate and long-term cardiovascular side effects of cancer treatment. Paradoxically, improvements in therapy for cancer have given people sufficient life spans to put them at risk for the late effects of therapy. As part of their treatment, patients can receive a cocktail of different therapies — surgery, radiation, chemotherapy. We’re finding that these treatments, while effective at killing and controlling cancer cells, also cause damage to the various components of the cardiovascular system, which includes the lungs, the heart, and the skeletal muscle. Together, this leads to a dramatic decrease in patients’ ability to exercise and even perform normal activities of daily living.

We’ve also learned that cancer therapy leads to a significant reduction in patients’ cardiovascular reserve capacity — commonly known as your fitness level — and it appears to stay impaired even years after therapy. In fact, we’ve found that even a short course of chemotherapy has the same impact on the cardiovascular system as ten years of normal aging. That’s the bad news. The good news is that in our clinical trials, we’re discovering that these effects can be completely mitigated in individuals who participate in our structured exercise training prescriptions.

Our second major focus is understanding and harnessing the potent therapeutic properties of exercise as a form of cancer treatment to prevent recurrence and even help conventional or novel cancer drug therapies work more effectively. We want to discover if and how exercise impacts tumor biology, both in the early and advanced stages of disease.

We’re actually trying to approach the development and testing of exercise as you’d think about the development of a new drug. The drug we’re testing just happens to be called exercise, but I believe that the way we test it should be no different. In our program, we are trying to adopt, whenever possible, the same type of sequential study steps with similar types of endpoints that oncologists and cancer biologists use in the development of new targeted therapies — we think of it as precision exercise treatment.

Is there a project that stands out as an example of this approach?

Here’s a good example. We’re interested in the testing the efficacy of exercise across the entire cancer trajectory, from prevention to advanced disease. To this end, we are about to launch a study looking at the early events in cancer.  When we see patients in clinic — after they've been diagnosed — a lot of the early events in the development of the disease have already occurred. I want to look at how exercise might be affecting some of these very early events.

To do this, we plan to perform a randomized controlled trial in women diagnosed with atypia [abnormal changes within the breast tissue]. These changes put them at significantly higher risk of developing invasive breast cancer. One hundred women will be assigned to a low, medium, or high dose of six months of supervised aerobic training — treadmill walking — low being 75 minutes a week, medium being 150 minutes, high being 300 minutes. The fourth arm, the control group, will be women who will receive the usual standard of care. All our aerobic training sessions are individualized to participants based on their fitness levels, which we measure at the beginning of the program using a sophisticated exercise stress test.

Before randomization, the participants will undergo a battery of assessments including a core biopsy of the normal breast tissue. After six months, the biopsy will be repeated and we will be able to evaluate, for the first time, whether aerobic training lowers the expression of genes in the normal breast tissue that are known to promote breast cancer and what the optimal dose of exercise is to stimulate these changes. What is also unique about this study is that we’ll be performing a study in mice that is the mirror image of the human clinical trial, known as a co-clinical trial. Using this approach, we’ll be able to learn things in the mouse study that will inform analyses in the human trial. To my knowledge, this is the first study ever to adopt this approach in clinical exercise science in any chronic condition. 

Similarly, we’re going to be starting a randomized clinical trial in men with early-stage prostate cancer who are part of MSK’s active surveillance program. In this approach, treatments such as surgery or radiation therapy are deferred because tests show that the tumor is currently not life threatening or is at low risk of progressing. Our trial is going to test the efficacy of 24 weeks of supervised aerobic exercise versus the usual care on the prostate microenvironment [the cellular environment in which a tumor exists] and cancer-related anxiety among these men. Again, to my knowledge, this will be the first trial to study the effects of exercise on changes in the tumor itself.

Findings from both these studies will provide unique insights into the effects of exercise on tumor and tissue biology as well as the biologic mechanisms underpinning these effects. This will help us design future studies as well as optimize the efficacy of exercise.

You’re also interested in cancer recurrence and metastatic disease and the potential impact of exercise in these circumstances.

I am. I’m very interested in prevention of recurrence and even the role of exercise in individuals with advanced disease. We are starting to explore if and how exercise might affect the course of disease in these populations.

In terms of metastasis, I think exercise not only changes things like the breast tissue but also alters the microenvironments in tissues such as the lung and bone marrow — those places in the body where metastatic cancer cells may be asleep [dormant]. I believe exercise may be able to actually change the microenvironment of such tissues to keep metastatic cancer cells asleep for longer — and perhaps even permanently. This is an area we’re studying collaboratively with various colleagues at MSK.

Your work spans both laboratory and clinical research.

It does. Along with clinical studies in patients, we’re also building a robust laboratory research program. Among the things we’re doing is working with mouse models as well as zebrafish (in collaboration with the Richard White laboratory in the Sloan Kettering Institute) to study what’s going on at the molecular level to better elucidate the effects and underlying mechanisms of exercise training on cancer initiation and progression.

You joined MSK in February 2014. How do you feel about your experience so far?

My expectations have already been far exceeded. Across the board — from oncologists to the clinical trials office and various administrative bodies — the support has been nothing short of incredible. MSK is designed in such a way that everybody feels connected and colleagues are extremely approachable. The reason I came to MSK is because our program goal is to make exercise therapy part of the standard of care for people with cancer. To do this, we need to do the best science and build a convincing evidence base, and that requires that we be at the best cancer hospital. MSK is that place!