Why muscle mass matters for cancer: the metabolic case for resistance training
When most people think about exercise and cancer, they think about cardiovascular activity — walking, cycling, swimming. Aerobic exercise has the strongest evidence base and the highest profile in cancer research. But there is a parallel story, less often told, about muscle tissue specifically: what it does metabolically, why losing it is dangerous, and why resistance training deserves a dedicated place in any evidence-based approach to cancer prevention and recovery.
This post is about the metabolic case for building and maintaining muscle mass — and what the evidence says about its relevance to cancer risk and treatment outcomes.
Muscle is not just for movement
Skeletal muscle is the largest metabolic organ in the body. It is responsible for the majority of insulin-stimulated glucose uptake — meaning it is the primary tissue through which blood sugar is cleared after a meal. When muscle mass is high and muscle tissue is metabolically active, glucose is efficiently taken up from the bloodstream, insulin sensitivity is maintained, and circulating insulin levels remain low.
When muscle mass is low — a condition known as sarcopenia — this glucose clearance capacity is reduced. Blood sugar rises higher after meals, the pancreas secretes more insulin to compensate, and chronically elevated insulin and IGF-1 (insulin-like growth factor 1) levels result. Both insulin and IGF-1 are growth factors: they signal cells to proliferate, suppress apoptosis, and activate the mTOR pathway — the same metabolic pathway that drives cancer cell growth in multiple tumour types.
This is the metabolic logic underpinning the connection between muscle mass and cancer: it is not simply that exercise burns calories or improves fitness. It is that skeletal muscle is the primary buffer against the hyperinsulinaemia and IGF-1 elevation that drive cancer-promoting metabolic signalling.
What the evidence shows
The CHALLENGE trial, published in the New England Journal of Medicine in 2025, randomised 889 patients with resected colon cancer who had completed chemotherapy to either a structured three-year exercise programme or usual care. The exercise programme was not purely aerobic — it combined structured aerobic activity with resistance training, specifically because the research team recognised that muscle preservation and development were central to the metabolic benefits they were targeting.
The results were striking: patients in the exercise arm had a 6.4 percentage point improvement in five-year disease-free survival and a 7.1 percentage point improvement in eight-year overall survival. These are among the largest survival benefits ever demonstrated for a lifestyle intervention in an oncology randomised controlled trial.
Whilst the CHALLENGE trial did not isolate the resistance training component from the aerobic component, the biological rationale for resistance training’s contribution is well established. Resistance exercise is uniquely effective at building and maintaining skeletal muscle mass, improving insulin sensitivity, and lowering circulating IGF-1 levels — the precise metabolic targets most relevant to cancer risk.
The American Cancer Society guidelines for cancer survivors, published in CA: A Cancer Journal for Clinicians in 2022, explicitly recommend resistance training as a component of exercise for cancer survivors — not simply aerobic activity. The guidelines cite evidence that muscle-strengthening exercise improves body composition, insulin sensitivity, fatigue, and quality of life in cancer survivors, and note that loss of muscle mass during and after cancer treatment is a significant independent predictor of poorer outcomes.
Sarcopenia and cancer outcomes
Sarcopenia — clinically low muscle mass — is increasingly recognised as an independent prognostic factor in cancer. Multiple prospective studies across tumour types including colorectal, breast, lung, and pancreatic cancer have found that patients with sarcopenia at diagnosis have worse treatment tolerance, higher rates of chemotherapy toxicity, higher complication rates after surgery, and poorer overall survival — independent of their tumour stage and treatment type.
The mechanism is partly pharmacological: chemotherapy dosing is often based on body surface area rather than lean mass, meaning sarcopenic patients with relatively high fat mass may receive disproportionately high doses relative to their lean tissue. This increases toxicity risk. It is also partly immunological: muscle tissue is a reservoir of glutamine, the primary fuel source for rapidly dividing immune cells. Low muscle mass limits the immune system’s capacity to mount an anti-tumour response.
The perimenopause connection
This is particularly relevant to women in perimenopause and beyond. Oestrogen plays a significant role in maintaining muscle mass and muscle quality — it supports satellite cell activity (the stem cells that repair and build muscle) and reduces inflammation within muscle tissue. As oestrogen declines during perimenopause, muscle loss accelerates. Women in their 40s and 50s can lose muscle mass at rates of 1–2% per year without targeted resistance training.
This age-related muscle loss — combined with the metabolic consequences of reduced insulin sensitivity — means that the perimenopausal decade is precisely when resistance training becomes most important, not least. Building muscle during this period is both a cancer-risk reduction strategy and a long-term investment in metabolic health, bone density, and functional independence.
What this means in practice
Resistance training two to three times per week is the foundation. The evidence supports structured resistance exercise — using bodyweight, resistance bands, free weights, or gym machines — targeting all major muscle groups. This does not require a gym; compound bodyweight movements (squats, lunges, press-ups, rows) are sufficient to build and maintain meaningful muscle mass when performed with sufficient effort.
Progressive overload matters. Muscle responds to challenge. To continue building and maintaining muscle, the resistance or difficulty must increase progressively over time. This is the fundamental principle of resistance training and the reason that comfortable, low-effort exercise — whilst better than nothing — does not produce the same metabolic benefits as training that genuinely challenges the muscle.
Protein intake supports muscle building. Resistance training stimulus requires adequate protein to convert into muscle tissue. Current evidence supports a protein intake of approximately 1.6–2.0 grams per kilogram of body weight per day for people engaged in regular resistance training — higher than general population recommendations, and higher still for older adults in whom muscle protein synthesis is less efficient. Distribute protein intake across meals rather than concentrating it in one sitting.
Combine with aerobic exercise. The CHALLENGE trial used a combined programme, and the evidence for aerobic exercise in cancer outcomes is strong and distinct from resistance training. The two are complementary, not competing. Aim for both: structured resistance training two to three times per week alongside at least 150 minutes of moderate aerobic activity per week.
If you are in or after cancer treatment, seek specialist guidance. A cancer-informed exercise physiologist can design a resistance programme that is safe around surgery, chemotherapy, or radiation — accounting for bone metastases, port placement, lymphoedema risk, and fatigue. Exercise during treatment is generally safe and beneficial, but individual adaptation matters.
What the evidence does not show
The evidence does not yet establish the precise dose of resistance training — frequency, volume, intensity — that optimises cancer outcomes. The CHALLENGE trial used a supervised, structured programme that most people do not have access to in routine life. How closely an unsupervised home programme replicates those benefits is not yet fully established.
The evidence also does not tell us that resistance training alone, without dietary and other lifestyle changes, produces meaningful cancer risk reduction. The metabolic benefits of muscle mass are most pronounced when combined with a whole-food dietary pattern that maintains stable blood sugar and reduces systemic inflammation. Resistance training is one component of a broader metabolic strategy, not a standalone intervention.
The bottom line
Skeletal muscle is not just structural — it is the body’s primary organ of metabolic regulation. Low muscle mass drives the hyperinsulinaemia and IGF-1 elevation that promote cancer cell growth; high muscle mass keeps these metabolic signals in check. The CHALLENGE trial demonstrated that a combined exercise programme — including resistance training — produces a clinically meaningful improvement in cancer survival. For perimenopausal women experiencing age-related muscle loss, resistance training is both the most timely and the most evidence-aligned exercise investment available.
Scientific references
- Courneya KS, et al. Exercise and colon cancer survival: the CHALLENGE randomised trial. New England Journal of Medicine. 2025. DOI: 10.1056/NEJMoa2502760
- Rock CL, et al. American Cancer Society guideline for diet and physical activity for cancer survivors. CA: A Cancer Journal for Clinicians. 2022. PMID: 35294043
- Patel AV, et al. American Cancer Society guideline for diet and physical activity for cancer prevention. CA: A Cancer Journal for Clinicians. 2020;70(4):245–271. DOI: 10.3322/caac.21591
- Mustian KM, et al. Comparison of pharmaceutical, psychological, and exercise treatments for cancer-related fatigue: a meta-analysis. JAMA Oncology. 2017;3(7):961–968. DOI: 10.1001/jamaoncol.2016.6914
This article is written for educational and informational purposes only. It is not intended as medical advice and should not be used to diagnose, treat, prevent, or cure any medical condition, including cancer. If you have a cancer diagnosis or are undergoing treatment, please discuss any lifestyle or dietary changes with your oncologist or medical team before making them. The studies cited reflect current research at the time of writing; the field is evolving rapidly and findings may be updated or superseded. Chloe Archard is a nutritional health coach, not a medical doctor.
