The goal of this 3 year project is to train the applicant in novel research techniques as he conducts a series of experiments designed to establish the relationship between ovarian cancer-derived inflammation, social isolation, and depressive and anxious symptoms in an animal model of the disease. This training is motivated by the high rates of depression and anxiety in ovarian cancer patients, which affect their treatment decisions, compliance to medical regimens, and quality of life, and is not adequately addressed by current treatments. To achieve this goal, the applicant will be mentored at two different institutions by experts in the fields of behavioral neuroscience, clinical psychology and tumor biology, and will learn surgical techniques, pharmacologic manipulations, and the use of small interfering RNA (siRNA) in vivo. The anticipated outcome of this project is the identification of key molecular and psychosocial mediators of depressive and anxious symptoms in ovarian cancer, possibilities for new pharmacologic and behavioral interventions in ovarian cancer patients, and the establishment of an animal model of depressive and anxious symptoms in ovarian cancer. Further, this project will advance NCI's mission statement to train promising scientists in cancer related research. The proposed research has several strengths: it approaches the issue of symptoms of negative affect in ovarian cancer from the novel perspective of cytokine-induced sickness behavior, will use an immunocompetent animal model of ovarian cancer which closely mimics the trajectory of the disease trajectory, and considers both molecular and psychosocial mediators of symptoms of negative affect. The work will test the hypotheses that depressive and anxious symptoms in ovarian cancer patients are due, in part, to evolutionarily conserved patterns of sickness behavior, and that cancer-derived inflammation is exacerbated by social isolation. The applicant will learn to apply cytokine antagonists and siRNA to the periphery and central nervous system of animals with induced tumors of the ovary to determine if depressive and anxious symptoms can be attenuated. In the second phase of the project, the applicant will conduct experiments to determine if cancer-derived inflammation can be modulated by social isolation. This will be under the guidance of the sponsor and co-sponsors who have considerable expertise in all the techniques that will be applied, as well as successful track record of mentoring former trainees. The project will include a mentored research program at M.D. Anderson in which the applicant will learn to apply siRNA for gene modulation in animal models of ovarian cancer from an established expert, followed by execution of the above mentioned experiments at the University of Iowa.
Ovarian cancer is characterized by a high incidence of depression, which may affect decision- making, treatment adherence, and quality of life. The current proposed research will clarify the role that ovarian cancer can play in the ontogeny of depressive symptoms. This research holds the possibility of identifying novel therapeutic targets for depression in patients with ovarian cancer.
|Schrepf, Andrew; O'Donnell, Michael A; Luo, Yi et al. (2016) Inflammation and Symptom Change in Interstitial Cystitis or Bladder Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study. Urology 90:56-61|
|Schrepf, Andrew; Lutgendorf, Susan K; Pyter, Leah M (2015) Pre-treatment effects of peripheral tumors on brain and behavior: Neuroinflammatory mechanisms in humans and rodents. Brain Behav Immun 49:1-17|