February 3, 2023 | 6 minute read

The search for ways to enhance cancer treatment – improving effectiveness and reducing its negative effects – was addressed in several presentations at the most recent AICR Research Conference.

Cancer treatments today are increasingly designed to target and disrupt specific pathways that are commonly abnormal in cancers. Research is now underway to see if particular diets may best support some cancer treatments.

Here are two examples, discussed in presentations at the 2022 AICR Research Conference, that highlight progress toward this goal.

Can Diet Influence the Gut Microbiome to Improve Response to Treatment?

Pioneering research has shown that gut microbes can influence the effectiveness of cancer immunotherapy treatment. The short-chain fatty acids that gut microbes produce from dietary fiber show potential to shape anti-tumor immune function. These fatty acids act as signaling molecules and regulators of gene expression.

In her presentation at the AICR Research Conference, Jessica Fessler, PhD, of Stanford University, presented research on how diet might change the gut microbiome in ways that improve response to immunotherapy.

In a 10-week intervention trial in healthy adults, some were assigned to a high-fiber diet with no fermented foods, others to a diet with multiple servings of fermented foods daily but no increase in dietary fiber.

• The high-fiber diet increased density of gut microbes and production of short-chain fatty acids, but did not affect the variety of microbes in the gut – referred to as microbiome diversity. (Researchers conducting the study noted that, since analysis of stools showed that microbiome remodeling was occurring, six weeks on the diet may have been too short to see full effects.)
• The diet high in fermented food increased the diversity of microbes within an individual’s microbiome. It also decreased inflammatory proteins that have been associated with chronic inflammation. Yogurt, kombucha, sauerkraut, kimchi, and pickled vegetables were the fermented foods most often consumed.

Given the distinct responses of participants to the two diets, more research is needed to see whether dietary fiber and fermented foods could work together even more powerfully to influence the gut microbiota and immune system. If so, then whether such diets might improve effectiveness of immunotherapy is an exciting possibility that needs to be studied.

Take-Home for Today: Promising, but don’t jump ahead of the evidence
Following the naturally high-fiber diet that AICR recommends for lower cancer risk also seems to support a gut microbiome that promotes health in many ways. And it’s possible that fermented foods may be beneficial, although much more research is needed.

Much of the work in how changing gut microbes influences immune function and immune response has been done in studies using mice. Researchers have not identified which bacteria help or how they do it, and it’s clear that individual strains of the same bacteria act differently. It’s premature to jump to commercial products such as probiotics in hopes of improving response to cancer treatment based on limited findings. Another caveat is that older adults and others receiving some types of cancer treatment can develop a weakened immune system, making them more vulnerable to infections like foodborne illnesses. For them, probiotics and even some fermented foods have the potential to pose risk.

Insulin Affects Response to Some Cancer Treatments

One of the most common questions oncology dietitians hear involves how sugar might “feed” cancer. Actually, noted Lewis Cantley, MD, PhD, of Harvard Medical School, blood levels of insulin are far more significant than levels of sugar in the blood when it comes to cancer cells. For decades, Dr. Cantley has studied a type of enzyme known as PI3K.

The PI3K signaling pathway affects cancer cell growth, survival, and ability to spread. Genetic mutations that increase PI3K signaling are common in cancer, and insulin activates signaling through this pathway.

PI3K inhibitors are a type of targeted cancer chemotherapy that block this signaling pathway, reducing cancer cells’ (with mutated PI3K) ability to take up sugar from the blood. However, in response to a high carbohydrate meal, blood sugar rises, prompting the body to increase production of insulin. Higher insulin levels then re-activate the PI3K pathway, “working against” the effects of the targeted cancer therapy.

This has prompted scientists to question whether people who have a mutation in genes regulating PI3K levels or function would benefit from a low-carbohydrate diet. In theory, this would avoid surges in circulating insulin and thus help PI3K inhibitor treatment work more effectively.

Cantley presented research from a laboratory study in which a ketogenic diet combined with PI3K inhibitor treatment significantly increased treatment effectiveness even more than medications that control blood sugar by reducing insulin.

Take-home Points: Promising, but don’t jump ahead of the evidence
Since insulin resistance and PI3K mutations are relatively common, being able to make cancer treatments that target this PI3K pathway more effectively holds lots of promise.

However, it’s important to note that this research is still in early stages:

• Diets designed to lower insulin levels– whether through a ketogenic or low-carbohydrate diet, or through decreased calories or intermittent fasting – have not yet demonstrated improvement in cancer-specific outcomes in humans, note Sherry Shen, MD, and Neil Iyengar, MD, of Memorial Sloan Kettering. “Thus these strategies cannot yet be recommended as part of routine cancer care in patients with metastatic disease.”
• If there are benefits of a low-carbohydrate diet in PI3K inhibitor cancer treatment, that doesn’t indicate benefits during other types of treatment.
• In some intervention trials, ketogenic diets during PI3K inhibitor treatment increased weight loss. For some people, weight loss may be safe during cancer treatment. But research has shown that if weight loss leads to significant loss of lean tissue like muscle, this is associated with worse cancer outcomes (even in people who have overweight or obesity).

Asked what these findings might mean about a ketogenic diet as a way to reduce cancer risk, Cantley emphasized that at least half of cancers do not have the mutation that this diet targets. And a diet high in vegetables, fruits, whole grains, and beans lowers overall cancer risk.

Progress One Step at a Time

In the future, as treatment increasingly targets specific cancer pathways, studies may identify targeted approaches to diet and physical activity that improve outcomes, too.

Research progresses one step at a time. Human observational studies show associations, but can’t prove cause-and-effect. Laboratory studies demonstrate mechanisms for effects, but can’t prove that they occur in people. Intervention trials in people show whether changes in diet, activity or treatment improve results. But even then, research needs to explore whether benefits occur in everyone, or whether those changes may be less effective or even counterproductive in some people.

For now, we are clearly at the beginning of the journey exploring how diet and physical activity can optimize cancer treatment.