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Developing dietary interventions as therapy for cancer

Nature Reviews Cancer volume 22, pages 452–466 (2022)Cite this article

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Abstract

Cancer cells acquire distinct metabolic preferences based on their tissue of origin, genetic alterations and degree of interaction with systemic hormones and metabolites. These adaptations support the increased nutrient demand required for increased growth and proliferation. Diet is the major source of nutrients for tumours, yet dietary interventions lack robust evidence and are rarely prescribed by clinicians for the treatment of cancer. Well-controlled diet studies in patients with cancer are rare, and existing studies have been limited by nonspecific enrolment criteria that inappropriately grouped together subjects with disparate tumour and host metabolic profiles. This imprecision may have masked the efficacy of the intervention for appropriate candidates. Here, we review the metabolic alterations and key vulnerabilities that occur across multiple types of cancer. We describe how these vulnerabilities could potentially be targeted using dietary therapies including energy or macronutrient restriction and intermittent fasting regimens. We also discuss recent trials that highlight how dietary strategies may be combined with pharmacological therapies to treat some cancers, potentially ushering a path towards precision nutrition for cancer.

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Fig. 1: Nutrient utilization in cancer.
Fig. 2: Tissue-specific metabolism.
Fig. 3: Development progress for dietary interventions for cancer.

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Acknowledgements

This work was supported, in part, by National Institutes of Health (NIH) K08CA230318 (M.D.G.), 2020 AACR–The Mark Foundation for Cancer Research ‘Science of the Patient’ (SOP) Grant Number 20-60-51-GONC (M.D.G.), NIH R35CA197588 (L.C.C.) and a grant from the Breast Cancer Research Foundation (L.C.C.).

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Weill Cornell Medicine, New York, NY, USA

    Samuel R. Taylor, John N. Falcone & Marcus D. Goncalves

  2. Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA

    Samuel R. Taylor, Lewis C. Cantley & Marcus D. Goncalves

  3. Weill Cornell/Rockefeller/Sloan Kettering Tri-I MD–PhD program, New York, NY, USA

    Samuel R. Taylor

Authors
  1. Samuel R. Taylor
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  2. John N. Falcone
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  3. Lewis C. Cantley
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  4. Marcus D. Goncalves
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Contributions

S.R.T., J.N.F. and M.D.G. researched data for the article and wrote the article. All authors contributed substantially to discussion of the content, and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Marcus D. Goncalves.

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Competing interests

L.C.C. is a founder, shareholder and member of the scientific advisory board of Agios Pharmaceuticals and a founder and former member of the scientific advisory board of Ravenna Pharmaceuticals (previously Petra Pharmaceuticals). These companies are developing novel therapies for cancer. L.C.C. has received research funding from Ravenna Pharmaceuticals outside the covered work. L.C.C. and M.D.G. are co-founders and shareholders of Faeth Therapeutics, which are developing dietary and pharmacologic therapies for cancer. M.D.G. has received speaking and/or consulting fees from Pfizer Inc., Novartis AG, Petra Pharmaceuticals, Scorpion Therapeutics and Faeth Therapeutics. M.D.G.’s laboratory has received financial support from Pfizer Inc. outside the covered work. All other authors report no competing interests.

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Peer review information

Nature Reviews Cancer thanks Stephan Herzig, Ömer Yilmaz and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Glossary

Electromotive force

The electric potential generated by the position of charged molecules, such as when partitioned across a membrane.

ATP synthase

A mitochondrial enzyme that phosphorylates ADP to make ATP.

Ketone bodies

Metabolites such as β-hydroxybutyrate and acetoacetate, which are produced during hepatic fatty acid oxidation and can be used as energy substrates by some tissues.

Triple-negative breast tumours

Breast tumours with low levels of oestrogen receptor (ER), progesterone receptor and HER2 overexpression and/or amplification. Typically, these tumours carry a worse prognosis than other types.

Proliferative phase of the endometrial cycle

The phase of the endometrial cycle in which the endometrial cells rapidly proliferate in preparation for possible implantation of a fertilized embryo.

Anapleurosis

Typically referring to the ‘refilling’ or ‘fuelling’ of the tricarboxylic acid (TCA) cycle with amino acids to drive biosynthetic reactions.

Ketosis

A metabolic state defined by low levels of insulin, high hepatic fatty acid oxidation and increased levels of circulating ketone bodies.

Metabolic dysfunction

A general term collating multiple abnormalities in glucose and lipid homeostasis such as dyslipidaemia, obesity, insulin resistance, glucose intolerance, diabetes and fatty liver disease.

Response Evaluation Criteria in Solid Tumours

(RECIST). A validated and consistent radiologic methodology to evaluate the activity and efficacy of new cancer therapeutics in solid tumours.

One-carbon metabolism

Referring to both the folate and methionine cycles that allow cells to generate one-carbon units for the biosynthesis of important anabolic precursors and for methylation reactions.

Eastern Cooperative Oncology Group

(ECOG). A standardized clinical scoring algorithm that describes a patient’s level of functioning in terms of their ability to care for themself, daily activity and physical ability (walking, working and so on).

Subjective Global Assessment

(SGA). A clinical scoring algorithm using information from a patient interview and physical examination that healthcare providers use to determine a person’s nutritional status.

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Taylor, S.R., Falcone, J.N., Cantley, L.C. et al. Developing dietary interventions as therapy for cancer. Nat Rev Cancer 22, 452–466 (2022). https://doi.org/10.1038/s41568-022-00485-y

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