Overview of exercise as a “biological intervention therapy” for cancer | Cancer Network

According to Nathan Goodyear, MD, incorporating structured exercise into traditional oncology treatments has the potential to reprogram the tumor immune microenvironment (TME) and significantly optimize treatment efficacy in cancer patients.

In an interview with CancerNetwork^®Dr. Goodyear emphasized that physical decline accelerates immunosenescence, immune depletion, and immune evasion, leading to rapid disease progression, often detected radiologically only after immunological collapse. Conversely, research has demonstrated that exercise acts as a powerful biological intervention that can extend lifespan. Reduced risk of recurrence. Increases the effectiveness of chemotherapy, immunotherapy, and surgery.

Data from the phase 3 CHALLENGE trial (NCT00819208) in patients with stage II and III colorectal cancer revealed a lower risk of death and fewer recurrences after a 3-year structured exercise program.¹ Furthermore, the OPTIMUS trial (NCT02950324) demonstrated that a short-term exercise program before surgery or in conjunction with chemotherapy increased CD8+ T cell infiltration and decreased immunosuppressive cells, effectively turning “cold” tumors “hot.”² According to Goodyear, maximizing these benefits requires integrative care professionals to precisely tailor physical activity to each patient’s specific disease stage, physical ability, and previous fitness level, treating exercise as a precise, customizable prescription rather than a general recommendation.

Goodyear is an integrative medicine physician at Williams Cancer Institute.

CancerNetwork: Can you elaborate on this idea that decreased fitness may be an early warning sign of cancer progression?

Goodyear: Looking at the progression of cancer, [often] What is seen radiologically. Imaging tests may show that the tumor is growing larger or the number of tumors is increasing. What if there were signs we could see before a major breakdown occurs? What if we could gain insight into early dysfunction? In fact, exercise is a window into ongoing breakdowns, especially when looking at the immune system. It is known that when humans become less active, their immune system weakens and immune fatigue increases. Basically, these two steps alone increase immunosenescence. Immunosenescence is the acceleration of aging.

What we see here is that as activity declines, it undergoes reverse upregulation of processes that promote accelerated aging, immune dysfunction, immunosenescence, immune depletion, and immune evasion. All this leads to rapid progression, which can eventually be seen radiologically, but here immunologically. For example, interleukin-6 levels begin to rise, but remain chronic. C-reactive protein is elevated and persists chronically. These are subtle markers. These are two markers that are available in routine clinical tests but are rarely evaluated.

In the context of activity, oncologists rarely ask about activity… But what if science showed that exercise was as good as many of the traditional cancer treatments that have been praised in human studies?[showing] That means it can extend your life. Reduce recurrence. Reduce metastasis. Increases the effectiveness of chemotherapy, immunotherapy, and surgery. That’s the reality.

What we have is the ability to monitor that ecosystem. That’s what research is showing us now. within [TME]It is an ecosystem that is not limited to [but] carried throughout the body. We have the ability to not only monitor it, but intervene with something as simple as exercise. It’s not just immunological. It is also metabolic and endocrinological ––[I am] Talk about circadian rhythms and sleep-wake cycles. These are all great adjuvants to the immune system. I believe that the immune system is the body’s main defense function that we need to work on. The standard treatment for the past 75 years or so has not involved the immune system, but when you involve the immune system, everything improves.

How can exercise optimize treatment outcomes for cancer patients?

There are studies showing that it is possible, but there are also studies showing that how That’s right. It is important to show not only the “what” but also the “how”. Now that it’s strong and solid, it’s also a way to increase the number of practitioners who incorporate exercise into their strategies.

There are several monitoring articles showing the “what”. One was announced at the venue 2025 American Society of Clinical Oncology (ASCO) Annual Meeting It is called CHALLENGE research. They looked at stage III and stage II colorectal cancer, where the key effects were fewer recurrences, fewer new cancers, and lower risk of death. [Investigators] One arm was compared to a three-year structured exercise program two days a week. I’m not talking about Iron Man. [Triathlon]––And in the second arm, we gave them some healthy information and said, “Here’s some healthy information. Live a healthy lifestyle through exercise.” It had a huge impact. In fact, if you look at these statistics, they are comparable to some of the well-known conventional cancer treatments. This does not mean replacing them. That is, if cancer is present, [we are not] Following this reductionist approach, we go from A to B to C to D. We have to start integrating this kind of cumulative therapy approach. If we could add something like exercise to chemotherapy [plus] Results are better if immunotherapy is given before surgery.

another [study]A study by the UK NHS called the OPTIMUS study followed these patients through a 12- or 16-week exercise program. It was a much smaller study that involved: [48] What they did was they tracked these patients in two segments. Each time was 8 weeks. One was chemotherapy, which improved the outcome, and the other was before surgery. They surgically removed the tumor and examined it. This is the “how”. They found an infiltration of CD8+ T cells and a decrease in immunosuppressive cells.

This study, of course, showed that exercise reprograms the TME. Well, they didn’t say this, and it is necessary [further validation]but it can also be framed as an exercise that heats up a cold tumor. This allows the infiltration and recruitment of immune cells within the TME, reprogramming them and allowing the immune system to engage. Here, we are primarily trying to transform an environment that tends to exclude immunity into one that can be utilized by the immune system. That’s the next level.

It gets even better. The other day, we had a patient whose stage IV cancer had returned. I often say, and this is true for all doctors, that even if we say something stupid, our patients will never forget it. The words you’re trying to say [sometimes] It just doesn’t come out… [Another] the doctor said [to a patient]“Your immune system is broken.” Patient [says to me]”How can I help you? My immune system is broken.” I said, “It’s not broken. The problem is that my immune system isn’t working. It doesn’t know it.” [how to attack malignant cells]”

Exercise reduces bone marrow-derived suppressor cells and regulatory T cells. These are important immunosuppressive cells that help create an immunosuppressive barrier within and around tumors. It frees up the immune system. The immune system may recognize tumors; [they] Coming – – there may be M2 macrophages, these myeloid-derived suppressor cells, and regulatory T cells – which are rejecting the immune system, which is alerted but shut out. Now, it’s not like your immune system is broken. The tumor prevents the immune system from working properly.

How can integrative care professionals best coordinate exercise to ensure patients are optimally positioned to receive maximum benefit?

Here is the exact nature of oncology. [finding] Deliver the right treatment to the right patient, in the right place and at the right time, with the right combination. If a patient came to you with sarcopenia, cachexia, stage IV advanced cancer, peripheral neuropathy from chemotherapy, you wouldn’t say, “Let’s do weight training three to four times a week. Let’s go outside and jog.” no. You have to say, “Okay. Now let’s move.”

beginning, [give a] Appropriate evaluation. What are the patient’s activities? [They may say,]
“I’m in a wheelchair all day” or “I’m in bed.” Start developing a strategy that says, “If you’re capable, let me do it for you…Let me walk you to the kitchen. Let me do a series of specific events that will help you move through your day.” Now, what we have is the ability to transform someone from a sedentary life to a life of actual movement. There will also be natural remedies. [moving]: Myokines, cytokines, immune system regulation.

It is acute rather than chronic. That’s one area where we get confused. Exercise increases interleukin-6 acutely, but not chronically. human research [show] Blocking interleukin-6 and epinephrine through exercise blocks the invasive ability of natural killer cells and causes tumor necrosis. Acute and chronic are very different as they relate to immune signaling.

So, in that patient example, we think, “Let’s go mobile now. Let’s build a strategy from there.” If someone comes in and says, “I’ve never worked out,” and they weigh 350 pounds, it’s kind of the same concept. Let’s get it [them] walking Then, once you’ve established that pattern, say, “I’m going to do some 1-pound dumbbells while walking one day a week.” [You must] Acute and chronic are different, resistance and aerobic exercise are related to the immune system, so you need to build it.

But let’s say an athlete comes. I had a patient who said, “I was a professional rower competing in the Olympics.” It doesn’t take long to say, “Okay, let’s have them do cardio three days a week. Let’s have them do strength training twice a week.” of [opposite] Here comes the problem. I have to get back on track. I say, “Look, you’re not training for the Olympics. We’re training your immune system. That’s totally different.”

We need to focus on the stage of the disease. This also plays a big role. For stage IV or III [disease]I’ll try a different approach. For stage I or II [disease]I take a different approach. We need to look at each person and see where they are. What can they do? Let’s be honest. Many of us are athletes, and many of us are not. Some people have a natural athletic ability, so in that respect we say, “We know you can do it, so let’s incorporate free weight resistance training.” But instead of just saying “please,” say “I want you to do this.”

What does that mean? “Am I going to go out there and be Arnold Schwarzenegger and bench press 300 pounds?” No, if you haven’t lifted dumbbells in a while, I want you to hold 10-pound dumbbells. I want you to do high reps and low weights so low that you’ll be embarrassed to be in the gym. [lifting]. I want you to do 3 sets. Take a 45 second break in between. Next, work on further strengthening your biceps, triceps, and lat lifts. Next, “lower body muscle groups, glutes, hamstrings, [gastrocnemius]”

What you need to do now is start teaching. It’s like we say, “From a surgical perspective, here’s what we’ll do to remove the tumor; from an oncological perspective, we’ll do the following.” As research is being done now, we need to do the same with exercise. [about] Show what and how. Exercise is not an alternative treatment. It is an independent biological intervention therapy. But when combined with other treatments, the treatments are surprisingly stackable or used sequentially to help patients not only beat cancer, but have better outcomes and live longer. That’s a concept I can dive into.

References

1. Corneya KS, Vardy JL, O’Callaghan CJ, et al. Systematic exercise after adjuvant chemotherapy for colon cancer. N English J Medicine 2025;393(1):13-25. doi:10.1056/NEJMoa2502760
2. Rayner CJ, Bartlett DB, Allen SK, et al. Prior rehabilitation during neoadjuvant chemotherapy enhances immune responses in esophageal adenocarcinoma tumors: a randomized controlled trial. J Sports Health Science 2025;14:101063. doi:10.1016/j.jshs.2025.101063