Epithelial ovarian cancer is the second most common gynecologic cancer. Because of poor survival for the majority of ovarian cancer patients, identification of factors contributing to disease progression is of utmost importance. Although a significant percentage of ovarian cancer patients respond well to initial chemotherapy, the success of treatment is limited by the development of chemo resistance, and the majority of patients relapse and die from recurrent disease. Our previous work has shown a variety of mechanisms by which biobehavioral factors (referring collectively to behavioral, social, and/or psychological factors and concomitant biologic processes) can directly affect key biological signaling mechanisms to enhance tumor growth and impair the immune response in ovarian cancer. Although the neuroendocrine stress hormones norepinephrine (NE) and cortisol have been shown to increase chemo resistance pre-clinically, little is known about the contribution of psychological and social processes to chemo resistance in the clinical setting of ovarian cancer. Based on compelling preliminary pre-clinical data in ovarian cancer, we propose that psychological and social processes and the neuroendocrine stress response will contribute to impairment of the chemotherapeutic response in ovarian cancer patients. Thus, this grant will focus on mapping psychological and social and neuroendocrine influences on disease progression in 178 women with high grade serous epithelial ovarian cancer, with particular attention to chemo resistance as a mechanism. This study is highly innovative as 1) contributions of biobehavioral processes to chemo resistance in human epithelial cell cancers in a clinical setting have not been examined, and 2) this is the first translational study using exosomes (tumor derived vesicles in peripheral circulation) to examine relationships between biobehavioral factors and tumor dynamics. Use of the exosome biomarker approach will provide a longitudinal window on tumor characteristics not otherwise available in the absence of repeated surgery. If initial response to chemotherapy could be enhanced or maintained for a longer duration, it could have substantial survival benefits. Thus findings that biobehavioral stress-related processes alter the response to chemotherapy would have significant implications for clinical management of ovarian patients, specifically the potential for adjunct use of behavioral or pharmacological interventions to delay the development of chemo resistance. Because chemotherapeutic response is closely linked to ovarian cancer survival, understanding biobehavioral impediments to maximum chemotherapeutic response is of great public health significance.

Public Health Relevance

Although many ovarian cancer patients respond well to initial chemotherapy, the majority develop chemo resistance, relapse, and die from recurrent disease. Biobehavioral stress-processes are known to impair the chemotherapeutic response in pre-clinical models of ovarian cancer, but little is known about biobehavioral factors and chemo resistance in clinical populations. This research investigates whether biobehavioral processes contribute to impaired chemotherapeutic response in ovarian cancer; positive findings will have substantial implications for clinical management of ovarian patients, specifically the potential fo adjunct use of behavioral or pharmacological interventions to delay the development of chemo resistance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA193249-03
Application #
9405852
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Green, Paige A
Project Start
2016-02-10
Project End
2020-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Iowa
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Allen, Julie K; Armaiz-Pena, Guillermo N; Nagaraja, Archana S et al. (2018) Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction. Cancer Res 78:3233-3242
Davis, Lauren Z; Cuneo, Michaela; Thaker, Premal H et al. (2018) Changes in spiritual well-being and psychological outcomes in ovarian cancer survivors. Psychooncology 27:477-483
Umamaheswaran, Sujanitha; Dasari, Santosh K; Yang, Peiying et al. (2018) Stress, inflammation, and eicosanoids: an emerging perspective. Cancer Metastasis Rev 37:203-211
Nagaraja, Archana S; Dood, Robert L; Armaiz-Pena, Guillermo et al. (2018) Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens. JCI Insight 3:
Armer, Jessica S; Clevenger, Lauren; Davis, Lauren Z et al. (2018) Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer. Cancer 124:3401-3408
Lutgendorf, Susan K; Thaker, Premal H; Arevalo, Jesusa M et al. (2018) Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma. Cancer 124:580-586
Nagaraja, Archana S; Dood, Robert L; Armaiz-Pena, Guillermo et al. (2017) Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens. JCI Insight 2:
Cuneo, Michaela G; Schrepf, Andrew; Slavich, George M et al. (2017) Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer. Psychoneuroendocrinology 84:139-142
Jutagir, Devika R; Blomberg, Bonnie B; Carver, Charles S et al. (2017) Social well-being is associated with less pro-inflammatory and pro-metastatic leukocyte gene expression in women after surgery for breast cancer. Breast Cancer Res Treat 165:169-180
Lutgendorf, Susan K; Shinn, Eileen; Carter, Jeanne et al. (2017) Quality of life among long-term survivors of advanced stage ovarian cancer: A cross-sectional approach. Gynecol Oncol 146:101-108

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