Grant Number:	5R35CA283926-02 Interpret this number
Primary Investigator:	Mandelblatt, Jeanne
Organization:	Georgetown University
Project Title:	Social Determinants of Health as Transducers of Cellular Aging: a New Multi-Level Paradigm to Reduce Survivorship Disparities at the Intersection of Cancer and Aging
Fiscal Year:	2024

By 2030, three-quarters of the 22 million US cancer survivors will be 65 and older and the number of older Hispanic and Black survivors will have grown three times faster than Whites. These shifting demographics are driving a crisis in cancer care due to a paucity of evidence to guide care for older survivors, especially older racial/ethnic survivors for whom data is virtually lacking. Filling these gaps will require an understanding of several complex multidirectional relationships at the intersection of health disparities, aging and cancer. Compared to older White survivors, older racial/ethnic minority survivors have had more lifetime exposures to adverse social determinants of health. These exposures accelerate aging processes. Aging increases the risk of developing cancer through accumulated damage and mutations. Cancer and its therapies, in turn, are disease drivers of aging. Together, these intersecting forces are likely to exacerbate current racial/ethnic cancer disparities in the health and quality of life of older survivors. The vision for this Outstanding Investigator Award is to fundamentally shift how we approach cancer disparities by providing a mechanistic understanding of the role of cellular aging in the relationships between social determinants of health and survivorship outcomes. I will use a conceptual model that integrates a multi-level disparities framework with oncology and geroscience perspectives to conduct research using transcriptomic and other -omics analyses, epigenetics, machine learning, mediation models, meta-synthesis and population simulation methods. The broad goals of my transdisciplinary research program are to: 1) discover cellular aging processes in large cohorts of older Black, Hispanic and White survivors that explain relationships between health determinants and quality of life (e.g., via stress signaling and downstream effects on cellular aging via inflammatory gene expression), 2) define mechanistic pathways suggested by cohort results and test the impact of interventions targeting those pathways in a preclinical model of cancer survivorship and 3) translate results to practice and policy. During my continuously NIH-funded research career, I have made transformative 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 translational continuum from preclinical to cohort studies and practice and policy. 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 that I lead and exceptional institutional commitment and infrastructure provide an exceptional environment. This Outstanding Investigator Award will provide me with the stability needed to accelerate knowledge in an understudied 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 for the burgeoning older minority survivor population and could to transform how we approach cancer disparities in the context of aging.




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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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
Related Citations

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; , .
EPub date: 2023-11-04 00:00:00.0.
PMID: 37924476
Related Citations