Grant Number:	2R01CA233777-09 Interpret this number
Primary Investigator:	Akinyemiju, Tomi
Organization:	Duke University
Project Title:	Orchid Renewal: Biological Embedding of Chronic Societal Stress in Ovarian Cancer
Fiscal Year:	2026

Abstract Ovarian cancer (OC) is one of the most lethal gynecologic malignancies in the US, with a five-year survival rate around 50%, and as low as 16% for patients with advanced high-grade serous disease. Despite recent therapeutic advancements, this disease remains highly fatal for most patients, highlighting an urgent need for studies of prognostic factors beyond stage and treatment access. Emerging evidence highlights that chronic societal stress is a potentially important but understudied contributor to OC prognosis. Chronic stress activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in inflammation and immune dysfunction—hallmarks of cancer and known drivers of tumor proliferation and metastasis. Conversely, resilience, the ability to adapt to adversity, may buffer these biological effects by modulating the stress response. This study will be the first to examine the full psychosocial-biological-clinical pathway linking chronic societal stress, inflammation and immune dysregulation to OC prognosis. We leverage the robust, population-based ORCHiD cohort of 1,500 ovarian cancer patients recruited from seven U.S. state registries, integrating rich patient-, area-, and clinical- level data with biospecimen collection (saliva, vaginal fluid, FFPE tumor tissue). We will integrate detailed data on societal stress, psychosocial factors, resilience and clinical outcomes, using validated instruments, with measures of systemic inflammation (from saliva), local inflammation (from vaginal fluid) and tumor immune function (from OC tumor tissues) to address the following aims: 1) Determine the association between chronic societal stress and OC prognosis accounting for psychosocial stress as a potential mediator; 2) Characterize the systemic and local inflammatory and tumor immune signatures in OC by tumor characteristics and chronic stress exposure, and 3) Evaluate how chronic societal stress and immune signatures jointly influence OC prognosis and whether resilience moderates this association. This innovative project breaks new ground by incorporating the bio-psycho-social framework in a robust, well-characterized cohort with clear translational impact. This study will not only advance fundamental understanding of stress biology in cancer but also lay the groundwork for therapeutic strategies tailored to the social and biological context of each patient.




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The Intersectionality between Race, Ethnicity, and Residential-Level Socioeconomic Status in Disparities of Head and Neck Cancer Outcomes: A SEER Study.
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