Despite the already dire impact of pancreatic cancer, a growing subset of patients with obesity exhibits an amplified risk of disease and worse outcomes. Mouse models have revealed that obesity is distinctly pathogenic, accelerating pancreatic ductal adenocarcinoma (PDAC) progression and inducing increased desmoplasia and myeloid cell infiltration in the tumor microenvironment. However, whether and how obesity-countering interventions, such as exercise, reverse the protumorigenic effects of obesity is incompletely understood. In this issue of Cancer Research, Pita-Grisanti and colleagues investigate the impact of physical activity (PA) in disrupting obesity-driven PDAC. Employing a variety of sophisticated models, including autochthonous genetically engineered mice, orthotopic syngeneic allografts, high-fat diet–induced obesity, and PA interventions in mice and humans, the authors found that PA impedes PDAC development in obese mice but does not impact the growth of advanced tumors. These antitumor effects correlated with reduced inflammation and fibrosis in the tumor microenvironment, a decline in high-fat diet–induced circulating inflammatory cytokines, and an increase in the IL15 signaling axis in white adipose tissue. Although adipose-targeted IL15 therapy was effective in suppressing advanced tumor growth in lean mice, obese mice were resistant to its therapeutic benefits. Together, the findings argue that PA delays obesity-driven early PDAC progression, implicating the preferential benefit of exercise as a preventative strategy. They further identify changes in obesity-associated local and systemic cytokine production as a possible mechanism for the antitumor effects of PA and help define context-specific determinants of response for emerging IL15-based immunotherapies.
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15 September 2024
In the Spotlight|
September 16 2024
Keep It Moving: Physical Activity in the Prevention of Obesity-Driven Pancreatic Cancer
Akin Sogunro
;
Akin Sogunro
1
Department of Genetics, Yale School of Medicine, Yale University, New Haven, Connecticut.
2
Yale Cancer Biology Institute, Yale University, West Haven, Connecticut.
3
M.D.-Ph.D. Program, Yale University, New Haven, Connecticut.
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Mandar D. Muzumdar
Mandar D. Muzumdar
*
1
Department of Genetics, Yale School of Medicine, Yale University, New Haven, Connecticut.
2
Yale Cancer Biology Institute, Yale University, West Haven, Connecticut.
3
M.D.-Ph.D. Program, Yale University, New Haven, Connecticut.
4
Program in Genetics, Genomics, and Epigenetics, Yale Cancer Center, Yale University, New Haven, Connecticut.
5
Department of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, Yale University, New Haven, Connecticut.
6
Molecular Cell Biology, Genetics, and Development Graduate Program, Yale Combined Program in the Biological and Biomedical Sciences, Yale University, New Haven, Connecticut.
*Corresponding Author: Mandar D. Muzumdar, Department of Genetics, Yale University, New Haven, CT 06520. E-mail: [email protected]
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*Corresponding Author: Mandar D. Muzumdar, Department of Genetics, Yale University, New Haven, CT 06520. E-mail: [email protected]
Cancer Res 2024;84:2935–7
Received:
June 11 2024
Accepted:
June 11 2024
Online ISSN: 1538-7445
Print ISSN: 0008-5472
©2024 American Association for Cancer Research
2024
American Association for Cancer Research
Cancer Res (2024) 84 (18): 2935–2937.
Article history
Received:
June 11 2024
Accepted:
June 11 2024
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Citation
Akin Sogunro, Mandar D. Muzumdar; Keep It Moving: Physical Activity in the Prevention of Obesity-Driven Pancreatic Cancer. Cancer Res 15 September 2024; 84 (18): 2935–2937. https://doi.org/10.1158/0008-5472.CAN-24-1474
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