Dietary Interventions and Cancer Treatment

Dietary interventions have moved from experimental curiosities to integral components of oncological research, exploring how modulation of nutrient intake can influence tumour biology, treatment efficacy and patient well-being. Strategies such as caloric restriction, intermittent fasting, fasting-mimicking diets, ketogenic regimens and protein-limited diets aim to induce metabolic stress in cancer cells while sparing normal tissues. These approaches exploit hallmark features of cancer metabolism, including heightened glycolysis and dysregulated growth signalling, to enhance sensitivity to chemotherapy, radiotherapy and immunotherapy. Beyond direct antitumour effects, dietary modulation can attenuate treatment-related toxicity, improve immune function and reduce systemic inflammation. Emerging evidence spans molecular mechanisms—involving alterations in insulin-like growth factor signalling, autophagy induction and mitochondrial function—to clinical outcomes, including response rates and quality-of-life measures. With ongoing translational and clinical investigations, dietary interventions promise globally applicable adjuncts that may optimise therapeutic windows, mitigate side effects and contribute to personalised cancer care.

Research from Nature Portfolio

Preclinical studies employing a fasting-mimicking diet in murine models have demonstrated that cyclical periods of nutrient restriction markedly enhance the efficacy of immune checkpoint blockade. Combined with agonists of co-stimulatory receptors such as OX40 and PD-L1 inhibitors, periodic fasting delayed melanoma progression, yielded trends towards improved control of lung carcinoma, and notably prevented immunotherapy-induced cardiotoxicity through reduction of myocardial fibrosis and systemic oxidative stress.

A multicentre, randomised phase 2 trial assessed a three-day fasting-mimicking diet alongside neoadjuvant chemotherapy in patients with HER2-negative breast cancer. Despite omission of dexamethasone, the intervention was well tolerated and was associated with higher rates of radiological and pathological response, alongside reduced chemotherapy-induced DNA damage in circulating T lymphocytes, supporting further exploration in larger trials.

Mechanistic investigations in colorectal cancer models have uncovered that short-term fasting upregulates the cholesterogenic enzyme FDFT1, leading to suppression of the AKT/mTOR/HIF1α axis. This shift inhibits aerobic glycolysis, curbs proliferation and elevates oxidative stress, effects that synergise with mTOR inhibitors to impede tumour growth and suggest novel molecular targets within diet-induced metabolic reprogramming.

Dietary Interventions and Cancer Treatment publication trend

The graph below shows the total number of articles in dietary interventions and cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

Fasting-mimicking diet: A low-calorie, low-protein and low-carbohydrate regimen designed to replicate the metabolic effects of water-only fasting while providing essential micronutrients.

Caloric restriction: A sustained reduction of total energy intake without malnutrition, shown to influence stress resistance pathways and slow tumour progression in preclinical models.

Immune checkpoint inhibitors: Therapeutic antibodies that block inhibitory receptors on T cells, such as PD-1 or CTLA-4, to potentiate anti-tumour immune responses.

AKT/mTOR/HIF1α signalling: A cellular pathway integrating growth factor and oxygen-sensing signals to regulate metabolism, proliferation and survival, often dysregulated in cancer.

Metabolic reprogramming: The alteration of energy production and biosynthetic pathways by cancer cells to support rapid proliferation and adapt to nutrient fluctuations.

References

1. Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential. Signal Transduction and Targeted Therapy (2024).
2. Fasting mimicking diet in mice delays cancer growth and reduces immunotherapy-associated cardiovascular and systemic side effects. Nature Communications (2023).
3. Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial. Nature Communications (2020).
4. Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT/mTOR/HIF1α pathway suppression. Nature Communications (2020).
5. Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer (2016).
6. When less may be more: calorie restriction and response to cancer therapy. BMC Medicine (2017).