Grant Number:	5R35CA283926-03 Interpret this number
Primary Investigator:	Mandelblatt, Jeanne
Organization:	Georgetown University
Project Title:	Investigations Connecting Cancer and Aging (I-Connect)
Fiscal Year:	2025

With advances in screening and treatment, cancer is becoming a chronic disease. By 2030, there will be 22 million cancer survivors living in the US and three-quarters of these survivors will be ages 65 and older. Over the life course, aging increases the risk of developing cancer through accumulated damage and mutations. Cancer and its therapies, in turn, can be disease drivers of additional aging, leading to long-term effects on quality of life and function, other chronic diseases and heterogeneity in population health outcomes. At present, we lack sufficient data about the complex bidirectional relationships between cancer and aging, leaving survivors and their oncology teams with insufficient evidence to guide care. The vision for this Outstanding Investigator Award is to use a unique cancer and aging laboratory spanning basic, clinical and population science to improve the health of cancer survivors. The broad goal of this laboratory is to collaborate across disciplines to study the bidirectional relationships between cancer and aging and use that knowledge to discover mechanistic pathways that can be leveraged to design, deliver and evaluate interventions to maintain and improve the health of cancer survivors. To achieve these goals, we use an overarching conceptual model that integrates knowledge about chronic disease, oncology and geroscience with tools from epigenetics,-omics analyses, machine learning and mediation, meta-synthesis and simulation statistical methods to: 1) evaluate how heterogeneity in biological aging processes and system dysregulation affect cancer and aging health outcomes in population cohorts, 2) identify mechanistic pathways suggested by cohort results and test the impact of interventions targeting those pathways in preclinical models of cancer survivorship and 3) apply results to clinical oncology care. During my continuously NIH-funded research career, I have made practice-changing contributions that support my proposed research program. There are few population scientists with the unique background and proven track record to successfully conduct this in-depth research program spanning the full scientific continuum from preclinical to cohort studies and clinical practice. Collaboration with scientists from outside my discipline will support my success and generate novel insights. The newly established Georgetown Lombardi Institute on Cancer and Aging REsearch (I-CARE) that I lead and exceptional institutional commitment and infrastructure provide an exceptional environment. This Outstanding Investigator Award provides the stability needed to accelerate knowledge in an important new research area with high public health significance and clinical relevance. Identification and testing of aging mechanistically-based interventions will support efforts to tailor clinical care and could change approaches to cancer survivorship and chronic disease management.




Establishing the Ecological Validity of Cognitive Patient Reported Outcome Measures in Breast Cancer Survivors: A Prospective Cohort Study.
Authors: Henneghan A.M. , Franco-Rocha O.Y. , Van Dyk K.M. , Paolillo E.W. , Haywood D. , Moore R.C. .
Source: Psycho-oncology, 2025 Nov; 34(11), p. e70324.
PMID: 41185103
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Creating a Mammography Conversation Aid for Shared Decision-Making Between Clinicians and Women Aged 75 and Older.
Authors: Schonberg M.A. , Stout N.K. , Stein S. , Corey M. , Jushchyshyn J. , Shah R. , Wolfson E. , Mandelblatt J.S. , Montori V.M. , Richman I. , et al. .
Source: Journal Of The American Geriatrics Society, 2025-04-15 00:00:00.0; , .
EPub date: 2025-04-15 00:00:00.0.
PMID: 40231782
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Impact of endocrine therapy regimens for early-stage ER+/HER2-breast cancer on contralateral breast cancer risk.
Authors: Sarkar S. , Schechter C. , Kurian A.W. , Caswell-Jin J.L. , Jayasekera J. , Mandelblatt J.S. .
Source: Npj Breast Cancer, 2025-03-26 00:00:00.0; 11(1), p. 30.
EPub date: 2025-03-26 00:00:00.0.
PMID: 40140385
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The chemotherapy agent doxorubicin induces CNS expression of Ascl1, a regulator of adult neurogenesis and differentiation.
Authors: Ng C.A.S. , Pedus M. , Lee M.F. , Kromer L.F. , Mandelblatt J. , Rebeck G.W. .
Source: Scientific Reports, 2025-03-21 00:00:00.0; 15(1), p. 9725.
EPub date: 2025-03-21 00:00:00.0.
PMID: 40118985
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Gerotherapeutics: aging mechanism-based pharmaceutical and behavioral interventions to reduce cancer racial and ethnic disparities.
Authors: Mandelblatt J.S. , Antoni M.H. , Bethea T.N. , Cole S. , Hudson B.I. , Penedo F.J. , Ramirez A.G. , Rebeck G.W. , Sarkar S. , Schwartz A.G. , et al. .
Source: Journal Of The National Cancer Institute, 2025-03-01 00:00:00.0; 117(3), p. 406-422.
PMID: 39196709
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Characterizing cancer-related cognitive impairments and impact on quality of life in women with metastatic breast cancer.
Authors: Henneghan A.M. , Van Dyk K.M. , Haywood D. , Patel M. , Franco-Rocha O.Y. , Bang S. , Longley T. , Tasker R. , Kaufmann T. , Paolillo E.W. , et al. .
Source: Breast Cancer Research And Treatment, 2025 Jan; 209(1), p. 125-138.
EPub date: 2024-09-13 00:00:00.0.
PMID: 39269553
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Reasons for Perceived Everyday Discrimination, Quality of Life, and Psychosocial Health of Breast Cancer Survivors: A Cross-Sectional Cluster Analysis.
Authors: Franco-Rocha O.Y. , Folh E. , Patel M. , Smits J.A.J. , Mohile S.G. , Asher A. , Van Dyk K.M. , Moore R.C. , Henneghan A.M. .
Source: Cancer Control : Journal Of The Moffitt Cancer Center, 2025 Jan-Dec; 32, p. 10732748251399963.
EPub date: 2025-11-20 00:00:00.0.
PMID: 41264928
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Deficit accumulation frailty index (DAFI) and treatment tolerability in AML: Data from CALGB 11001 and 11002 (Alliance).
Authors: Lai C. , Lee M. , Bobek O. , Le-Rademacher J. , Mandrekar S.J. , Roboz G.J. , Uy G.L. , Mandelblatt J. , Klepin H.D. .
Source: Blood Advances, 2024-11-27 00:00:00.0; , .
EPub date: 2024-11-27 00:00:00.0.
PMID: 39602659
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Shining a spotlight on sleep disturbance-related cognitive impairment and relevance to menopause.
Authors: Van Dyk K. , Carroll J.E. .
Source: Sleep, 2024-08-14 00:00:00.0; 47(8), .
PMID: 38894675
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Physical Activity and Cognition: Longitudinal findings from the Thinking and Living with Cancer Study.
Authors: Artese A.L. , Zhou X. , Tometich D.B. , Small B.J. , Ahles T.A. , Ahn J. , Bethea T.N. , Breen E.C. , Cohen H.J. , Extermann M. , et al. .
Source: Journal Of The National Cancer Institute, 2024-08-06 00:00:00.0; , .
EPub date: 2024-08-06 00:00:00.0.
PMID: 39107910
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The Aspirin Conundrum-Navigating Negative Results, Age, Aging Dynamics, and Equity.
Authors: Mandelblatt J.S. , Mainor C. , Hudson B.I. .
Source: Jama, 2024-05-28 00:00:00.0; 331(20), p. 1709-1711.
PMID: 38683570
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Alzheimer's disease-related biomarkers and cancer-related cognitive decline: the thinking and living with cancer study.
Authors: Mandelblatt J. , Dage J.L. , Zhou X. , Small B.J. , Ahles T.A. , Ahn J. , Artese A. , Bethea T.N. , Breen E.C. , Carroll J.E. , et al. .
Source: Journal Of The National Cancer Institute, 2024-05-24 00:00:00.0; , .
EPub date: 2024-05-24 00:00:00.0.
PMID: 38788675
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A scoping review of racial, ethnic, socioeconomic, and geographic disparities in the outcomes of older adults with cancer.
Authors: Gilmore N. , Grant S.J. , Bethea T.N. , Schiaffino M.K. , Klepin H.D. , Dale W. , Hardi A. , Mandelblatt J. , Mohile S. , Cancer and Aging Research Group .
Source: Journal Of The American Geriatrics Society, 2024-04-09 00:00:00.0; , .
EPub date: 2024-04-09 00:00:00.0.
PMID: 38593225
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The chemotherapeutic agent doxorubicin induces brain senescence, with modulation by APOE genotype.
Authors: Demby T. , Gross P.S. , Mandelblatt J. , Huang J.K. , Rebeck G.W. .
Source: Experimental Neurology, 2024 Jan; 371, p. 114609.
EPub date: 2023-11-07 00:00:00.0.
PMID: 37944881
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Using simulation modeling to guide policy to reduce disparities and achieve equity in cancer outcomes: state of the science and a road map for the future.
Authors: Mandelblatt J. , Meza R. , Trentham-Dietz A. , Heckman-Stoddard B. , Feuer E. .
Source: Journal Of The National Cancer Institute. Monographs, 2023-11-08 00:00:00.0; 2023(62), p. 159-166.
PMID: 37947330
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Population simulation modeling of disparities in US breast cancer mortality.
Authors: Mandelblatt J.S. , Schechter C.B. , Stout N.K. , Huang H. , Stein S. , Hunter Chapman C. , Trentham-Dietz A. , Jayasekera J. , Gangnon R.E. , Hampton J.M. , et al. .
Source: Journal Of The National Cancer Institute. Monographs, 2023-11-08 00:00:00.0; 2023(62), p. 178-187.
PMID: 37947337
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A health equity framework to support the next generation of cancer population simulation models.
Authors: Chapman C. , Jayasekera J. , Dash C. , Sheppard V. , Mandelblatt J. .
Source: Journal Of The National Cancer Institute. Monographs, 2023-11-08 00:00:00.0; 2023(62), p. 255-264.
PMID: 37947339
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Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.
Authors: Nakamura Z.M. , Small B.J. , Zhai W. , Ahles T.A. , Ahn J. , Artese A.L. , Bethea T.N. , Breen E.C. , Cohen H.J. , Extermann M. , et al. .
Source: Journal Of Cancer Survivorship : Research And Practice, 2023-11-04 00:00:00.0; , .
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