[R01] ORCHID Renewal: Biological Embedding of Chronic Societal Stress in Ovarian Cancer
Ente: National Cancer Institute
Scadenza: 2031-05-31
Importo max: 524.191 EUR
Paese: US
Descrizione
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.
Istituzione: DUKE UNIVERSITY
PI: Tomi F Akinyemiju
Progetto: 2R01CA233777-09
Settori: National Cancer Institute
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