Challenges and opportunities for modeling aging and cancer

Olga Anczuków¹, Susie Airhart², Jeffrey H Chuang³, Lisa M Coussens⁴, George A Kuchel⁵, Ron Korstanje², Sheng Li³, Anna Lisa Lucido³, Sandra S McAllister⁶, Katerina Politi⁷, Kornelia Polyak⁸, Timothy Ratliff⁹, Gary Ren², Jennifer J Trowbridge², Duygu Ucar³, Karolina Palucka¹⁰

Affiliations

¹ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Electronic address: olga.anczukow@jax.org.
² The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA.
³ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
⁴ Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
⁵ UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, USA.
⁶ Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA.
⁷ Departments of Pathology, and Medicine (Section of Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA.
⁸ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; The Ludwig Center at Harvard, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA.
⁹ Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA.
¹⁰ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Electronic address: karolina.palucka@jax.org.

PMID: 37001528
PMCID: PMC10185379
DOI: 10.1016/j.ccell.2023.03.006

Challenges and opportunities for modeling aging and cancer

Olga Anczuków et al. Cancer Cell. 2023.

. 2023 Apr 10;41(4):641-645.

doi: 10.1016/j.ccell.2023.03.006. Epub 2023 Mar 30.

Authors

Affiliations

¹ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Electronic address: olga.anczukow@jax.org.
² The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA.
³ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
⁴ Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR, USA; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
⁵ UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, USA.
⁶ Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA.
⁷ Departments of Pathology, and Medicine (Section of Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA.
⁸ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA; The Ludwig Center at Harvard, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA.
⁹ Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA.
¹⁰ The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Electronic address: karolina.palucka@jax.org.

PMID: 37001528
PMCID: PMC10185379
DOI: 10.1016/j.ccell.2023.03.006

Abstract

Age is among the main risk factors for cancer, and any cancer study in adults is faced with an aging tissue and organism. Yet, pre-clinical studies are carried out using young mice and are not able to address the impact of aging and associated comorbidities on disease biology and treatment outcomes. Here, we discuss the limitations of current mouse cancer models and suggest strategies for developing novel models to address these major gaps in knowledge and experimental approaches.

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Conflict of interest statement

Declaration of interests K. Polyak serves on the scientific advisory boards of Novartis, Vividion Therapeutics, Ideya Biosciences, and Scorpion Therapeutics; holds equity options in Scorpion Therapeutics; has received honorarium from Astra-Zeneca, New Equilibrium Biosciences, and Roche in the past 12 months; and receives sponsored research funding from Novartis. K. Politi is coinventor on a patent for EGFRT790M mutation testing issued, licensed, and with royalties paid from Molecular Diagnostics/Memorial Sloan Kettering Cancer Center. She reports research funding to her institution from AstraZeneca, Roche/Genentech, Boehringer Ingelheim, and D2G Oncology, and consulting for AstraZeneca and Jannssen. K. Palucka is a cofounder of Guardian Bio and holds equity and receives research support from Guardian Bio. She is a member of the scientific advisory board and holds equity from Cue Biopharma. She received research support from Merck in the past. O.A. has received research support from Sanofi and Pacbio in the past. J.J.T. receives patent royalties from Fate Therapeutics. She has also received research support from H3 Biomedicine, Inc. L.M.C. reports consulting services for Cell Signaling Technologies, AbbVie, the Susan G. Komen Foundation, and Shasqi; has received reagent and/or research support from Cell Signaling Technologies, Syndax Pharmaceuticals, ZelBio, Inc., Hibercell, Inc., Acerta Pharma, Prospect Creek Foundation, the Susan G. Komen Foundation, and National Foundation for Cancer Research; and has participated in advisory boards for Syndax Pharmaceuticals, Carisma Therapeutics, Inc., CytomX Therapeutics, Inc., Kineta, Inc., Hibercell, Inc., Cell Signaling Technologies, Alkermes, Inc., Genenta Sciences, Pio Therapeutics, Pty., Ltd., PDX Pharmaceuticals, Inc., NextCure, Guardian Bio, the AstraZeneca Partner of Choice Network, the Lustgarten Foundation, and the NIH/NCI-Frederick National Laboratory Advisory Committee.

Figures

**Figure 1.. Developing new models for age-related cancers.**
Key features to be modeled include molecular processes such as the impact of genetic diversity, the accumulation of mutations with age including mutations associated with clonal hematopoiesis, epigenetics, and post-transcriptional alterations, aging of the immune system, and age-related remodeling of the microenvironment, as well as environmental factors such as stress and obesity. Accounting for these features will improve models for testing therapeutic and prevention strategies. Inducible transgenic animals or spontaneous transplantable models would enable the study of tumors in older animals.

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References

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Challenges and opportunities for modeling aging and cancer

Affiliations

Challenges and opportunities for modeling aging and cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

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