Skip to main content
Grant Details

Grant Number: 5R01CA193249-03 Interpret this number
Primary Investigator: Lutgendorf, Susan
Organization: University Of Iowa
Project Title: Behavioral Influences on Ovarian Cancer Progression: Role of Chemoresistance
Fiscal Year: 2018
Back to top


Abstract

 DESCRIPTION (provided by applicant): 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.

Back to top


Publications

Stress, inflammation, and eicosanoids: an emerging perspective.
Authors: Umamaheswaran S. , Dasari S.K. , Yang P. , Lutgendorf S.K. , Sood A.K. .
Source: Cancer metastasis reviews, 2018 09; 37(2-3), p. 203-211.
PMID: 29948328
Related Citations

Life stress as a risk factor for sustained anxiety and cortisol dysregulation during the first year of survivorship in ovarian cancer.
Authors: Armer J.S. , Clevenger L. , Davis L.Z. , Cuneo M. , Thaker P.H. , Goodheart M.J. , Bender D.P. , Dahmoush L. , Sood A.K. , Cole S.W. , et al. .
Source: Cancer, 2018 Aug; 124(16), p. 3401-3408.
EPub date: 2018-06-15.
PMID: 29905941
Related Citations

Sustained Adrenergic Signaling Promotes Intratumoral Innervation through BDNF Induction.
Authors: Allen J.K. , Armaiz-Pena G.N. , Nagaraja A.S. , Sadaoui N.C. , Ortiz T. , Dood R. , Ozcan M. , Herder D.M. , Haemmerle M. , Gharpure K.M. , et al. .
Source: Cancer research, 2018-06-15; 78(12), p. 3233-3242.
EPub date: 2018-04-16.
PMID: 29661830
Related Citations

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens.
Authors: Nagaraja A.S. , Dood R.L. , Armaiz-Pena G. , Kang Y. , Wu S.Y. , Allen J.K. , Jennings N.B. , Mangala L.S. , Pradeep S. , Lyons Y. , et al. .
Source: JCI insight, 2018-06-07; 3(11), .
EPub date: 2018-06-07.
PMID: 29889660
Related Citations

Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma.
Authors: Lutgendorf S.K. , Thaker P.H. , Arevalo J.M. , Goodheart M.J. , Slavich G.M. , Sood A.K. , Cole S.W. .
Source: Cancer, 2018-02-01; 124(3), p. 580-586.
EPub date: 2017-11-07.
PMID: 29112229
Related Citations

Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer.
Authors: Cuneo M.G. , Schrepf A. , Slavich G.M. , Thaker P.H. , Goodheart M. , Bender D. , Cole S.W. , Sood A.K. , Lutgendorf S.K. .
Source: Psychoneuroendocrinology, 2017 Oct; 84, p. 139-142.
EPub date: 2017-06-30.
PMID: 28711723
Related Citations

Adrenergic-mediated increases in INHBA drive CAF phenotype and collagens.
Authors: Nagaraja A.S. , Dood R.L. , Armaiz-Pena G. , Kang Y. , Wu S.Y. , Allen J.K. , Jennings N.B. , Mangala L.S. , Pradeep S. , Lyons Y. , et al. .
Source: JCI insight, 2017-08-17; 2(16), .
EPub date: 2017-08-17.
PMID: 28814667
Related Citations

Changes in spiritual well-being and psychological outcomes in ovarian cancer survivors.
Authors: Davis L.Z. , Cuneo M. , Thaker P.H. , Goodheart M.J. , Bender D. , Lutgendorf S.K. .
Source: Psycho-oncology, 2018 02; 27(2), p. 477-483.
EPub date: 2017-08-04.
PMID: 28637083
Related Citations

Social well-being is associated with less pro-inflammatory and pro-metastatic leukocyte gene expression in women after surgery for breast cancer.
Authors: Jutagir D.R. , Blomberg B.B. , Carver C.S. , Lechner S.C. , Timpano K.R. , Bouchard L.C. , Gudenkauf L.M. , Jacobs J.M. , Diaz A. , Lutgendorf S.K. , et al. .
Source: Breast cancer research and treatment, 2017 Aug; 165(1), p. 169-180.
EPub date: 2017-05-30.
PMID: 28560656
Related Citations

Quality of life among long-term survivors of advanced stage ovarian cancer: A cross-sectional approach.
Authors: Lutgendorf S.K. , Shinn E. , Carter J. , Leighton S. , Baggerly K. , Guindani M. , Fellman B. , Matzo M. , Slavich G.M. , Goodman M.T. , et al. .
Source: Gynecologic oncology, 2017 07; 146(1), p. 101-108.
EPub date: 2017-05-17.
PMID: 28527672
Related Citations

Stress management, leukocyte transcriptional changes and breast cancer recurrence in a randomized trial: An exploratory analysis.
Authors: Antoni M.H. , Bouchard L.C. , Jacobs J.M. , Lechner S.C. , Jutagir D.R. , Gudenkauf L.M. , Carver C.S. , Lutgendorf S. , Cole S.W. , Lippman M. , et al. .
Source: Psychoneuroendocrinology, 2016 12; 74, p. 269-277.
EPub date: 2016-09-24.
PMID: 27689900
Related Citations

SSRI use and clinical outcomes in epithelial ovarian cancer.
Authors: Christensen D.K. , Armaiz-Pena G.N. , Ramirez E. , Matsuo K. , Zimmerman B. , Zand B. , Shinn E. , Goodheart M.J. , Bender D. , Thaker P.H. , et al. .
Source: Oncotarget, 2016-05-31; 7(22), p. 33179-91.
PMID: 27121207
Related Citations

Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis.
Authors: Nagaraja A.S. , Dorniak P.L. , Sadaoui N.C. , Kang Y. , Lin T. , Armaiz-Pena G. , Wu S.Y. , Rupaimoole R. , Allen J.K. , Gharpure K.M. , et al. .
Source: Oncogene, 2016-05-05; 35(18), p. 2390-7.
EPub date: 2015-08-10.
PMID: 26257064
Related Citations

Characteristics of 10-year survivors of high-grade serous ovarian carcinoma.
Authors: Dao F. , Schlappe B.A. , Tseng J. , Lester J. , Nick A.M. , Lutgendorf S.K. , McMeekin S. , Coleman R.L. , Moore K.N. , Karlan B.Y. , et al. .
Source: Gynecologic oncology, 2016 May; 141(2), p. 260-263.
EPub date: 2016-03-11.
PMID: 26968641
Related Citations

Adrenergic Stimulation of DUSP1 Impairs Chemotherapy Response in Ovarian Cancer.
Authors: Kang Y. , Nagaraja A.S. , Armaiz-Pena G.N. , Dorniak P.L. , Hu W. , Rupaimoole R. , Liu T. , Gharpure K.M. , Previs R.A. , Hansen J.M. , et al. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2016-04-01; 22(7), p. 1713-24.
EPub date: 2015-11-18.
PMID: 26581245
Related Citations




Back to Top