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(A) Cell loading and single cell array generation. (B) A representative CometChip image shows undamaged and damaged nucleoids and the mode of analysis used in this study. (C) Alkaline (global DNA damage) and neutral (double-strand break) CometChip assay optimization for detection of double-strand breaks (DSB), and single-strand breaks (SSB). HCT116 cells were treated with methylmethane sulfonate (MMS) and bleomycin (BLM) and analyzed in alkaline and neutral CometChip assays. Tail Moment is used as a DNA damage parameter. p < 0.05 was considered significant. Created with Biorender.com (accessed on 2 May 2024).
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Non-Hispanic Black breast cancer survivors have poorer outcomes than White survivors, but the biological mechanisms underlying these disparities are unclear. We discovered novel race-based differences in systemic DNA damage and repair activity among breast cancer survivors. This finding suggests DNA damage and repair are important ba...
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The central premise of this article is that a portion of the established relationships between social determinants of health and racial/ethnic disparities in cancer morbidity and mortality are mediated through differences in rates of biological aging processes. We further posit that using knowledge about aging could enable discovery and testing of new mechanism-based pharmaceutical and behavioral interventions (“gerotherapeutics”) to differentially improve the health of minoritized cancer survivors and reduce cancer disparities.
These hypotheses are based on evidence that lifelong differences in adverse social determinants of health contribute to disparities in rates of biological aging (“social determinants of aging”), with minoritized groups having accelerated aging (ie, a steeper slope or trajectory of biological aging over time relative to chronological age) more often than non-minoritized groups. Acceleration of biological aging can increase the risk, age of onset, aggressivity and/or stage of many adult cancers. There are also documented negative feedback loops whereby the cellular damage caused by cancer and its therapies act as drivers of additional biological aging. Together, these dynamic intersectional forces can contribute to differences in cancer outcomes between minoritized vs non-minoritized survivor populations.
We highlight key targetable biological aging mechanisms with potential applications to reducing cancer disparities and discuss methodological considerations for pre-clinical and clinical testing of the impact of gerotherapeutics on cancer outcomes in minoritized populations. Ultimately, the promise of reducing cancer disparities will require broad societal policy changes that address the structural causes of accelerated biological aging and ensure equitable access to all new cancer control paradigms.
