Mandelblatt Jeanne S, Antoni Michael H, Bethea Traci N, Cole Steve, Hudson Barry I, Penedo Frank J, Ramirez Amelie G, Rebeck G William, Sarkar Swarnavo, Schwartz Ann G, Sloan Erica K, Zheng Yun-Ling, Carroll Judith E, Sedrak Mina S
Georgetown Lombardi Institute for Cancer and Aging Research, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC, USA.
J Natl Cancer Inst. 2025 Mar 1;117(3):406-422. doi: 10.1093/jnci/djae211.
The central premise of this article is that a portion of the established relationships between social determinants of health and racial and ethnic disparities in cancer morbidity and mortality is 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 cancer survivors from minority populations 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 individuals from minoritized groups experiencing accelerated aging (ie, a steeper slope or trajectory of biological aging over time relative to chronological age) more often than individuals from nonminoritized groups. Acceleration of biological aging can increase the risk, age of onset, aggressiveness, and 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 survivors from minoritized vs nonminoritized populations. We highlight key targetable biological aging mechanisms with potential applications to reducing cancer disparities and discuss methodological considerations for preclinical 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.
本文的核心前提是,健康的社会决定因素与癌症发病率和死亡率方面的种族和民族差异之间已确立的部分关系是通过生物衰老过程速率的差异介导的。我们进一步假定,利用有关衰老的知识能够发现并测试基于新机制的药物和行为干预措施(“老年疗法”),以有差别地改善少数族裔癌症幸存者的健康状况并减少癌症差异。这些假设基于以下证据:健康方面不利的社会决定因素的终身差异导致生物衰老速率的差异(“衰老的社会决定因素”),与未被边缘化群体的个体相比,被边缘化群体的个体更常经历加速衰老(即,相对于实际年龄,生物衰老随时间的斜率或轨迹更陡)。生物衰老加速会增加许多成人癌症的风险、发病年龄、侵袭性和阶段。也有文献记载了负反馈回路,即癌症及其治疗造成的细胞损伤会成为额外生物衰老的驱动因素。这些动态的交叉力量共同作用,可能导致被边缘化群体与未被边缘化群体的癌症幸存者在癌症结局上出现差异。我们强调了可靶向的关键生物衰老机制及其在减少癌症差异方面的潜在应用,并讨论了在临床前和临床测试老年疗法对被边缘化群体癌症结局影响时的方法学考虑因素。最终,减少癌症差异的前景将需要广泛的社会政策变革,以解决生物衰老加速的结构性原因,并确保公平获得所有新的癌症控制模式。