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Bodywide ecological interventions on cancer

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Abstract

Historically, cancer research and therapy have focused on malignant cells and their tumor microenvironment. However, the vascular, lymphatic and nervous systems establish long-range communication between the tumor and the host. This communication is mediated by metabolites generated by the host or the gut microbiota, as well by systemic neuroendocrine, pro-inflammatory and immune circuitries—all of which dictate the trajectory of malignant disease through molecularly defined biological mechanisms. Moreover, aging, co-morbidities and co-medications have a major impact on the development, progression and therapeutic response of patients with cancer. In this Perspective, we advocate for a whole-body ‘ecological’ exploration of malignant disease. We surmise that accumulating knowledge on the intricate relationship between the host and the tumor will shape rational strategies for systemic, bodywide interventions that will eventually improve tumor control, as well as quality of life, in patients with cancer.

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Fig. 1: Paradigm shifts in cancer research and therapy.
Fig. 2: Molecules and pathways linking components of the bodywide ecosystem to the tumor microenvironment.
Fig. 3: Future management of patients with cancer.

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The paper does not contain any original or unpublished data.

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Acknowledgements

G.K. and L.Z. are supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR) – Projets blancs; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Institut National du Cancer (INCa); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Immunolife; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001. J.L.M. acknowledges the Transdisciplinary Research in Energetics and Cancer Research Training Workshop R25CA203650 and the MD Anderson Cancer Center (MDA) Center for Energy Balance in Cancer Prevention and Survivorship and is supported by ASCO/CCF, the Melanoma Research Alliance, the Elkins Foundation, Seerave Foundation, Rising Tide Foundation, the Mark Foundation for Cancer Research, MDA Melanoma SPORE Developmental Research Program Award, MDA Physician Scientist Program and MDA Moonshot Program. M.M. was supported by NIH grants U24 AI118644-05S1, R01CA257195 and R01CA254104 (Tumor macs), as well as by the Samuel Waxman Cancer Research Foundation. A.F. received ANR funding for IHU-B PRISM.

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G.K. wrote the first draft and then received major input from J.L.M., M.M., F.A. and L.Z. All authors have read, edited and approved the paper.

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Correspondence to Guido Kroemer.

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Competing interests

G.K. holds research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys and Vascage. G. K. consults for Reithera. G.K. is on the board of directors of the Bristol Myers Squibb Foundation France. G.K. is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. G.K. is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. G.K.’s brother, R.omano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. J. M. has served in advisory roles for BMS, Merck and Roche. M.M. reports grants from Regeneron, Inc, outside the submitted work. F.A. has grants and advisory roles (compensated to the hospital) for Daiichi Sankyo, Pfizer, Novartis, Astra Zeneca, Lilly and Roche. L.Z. has held research contracts with 9 Meters Biopharma, Daiichi Sankyo, and Pilege, was on the on the Board of Directors of Transgene, is a co-founder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. None of the funders had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Kroemer, G., McQuade, J.L., Merad, M. et al. Bodywide ecological interventions on cancer. Nat Med 29, 59–74 (2023). https://doi.org/10.1038/s41591-022-02193-4

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