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Grant Details

Grant Number: 5R01CA193249-05 Interpret this number
Primary Investigator: Lutgendorf, Susan
Organization: University Of Iowa
Project Title: Behavioral Influences on Ovarian Cancer Progression: Role of Chemoresistance
Fiscal Year: 2020


 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.


The Role of Psychologic Stress in Cancer Initiation: Clinical Relevance and Potential Molecular Mechanisms.
Authors: Falcinelli M. , Thaker P.H. , Lutgendorf S.K. , Conzen S.D. , Flaherty R.L. , Flint M.S. .
Source: Cancer research, 2021-10-15; 81(20), p. 5131-5140.
EPub date: 2021-07-15.
PMID: 34266894
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Rural residence is related to shorter survival in epithelial ovarian cancer patients.
Authors: Lutgendorf S.K. , Ramirez E. , Schrepf A. , Valentine M.C. , Charlton M. , Zimmerman M.B. , Goodheart M.J. , Zia S. , Sood A.K. , Thaker P.H. .
Source: Gynecologic oncology, 2021 Oct; 163(1), p. 22-28.
EPub date: 2021-08-13.
PMID: 34400004
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Mitochondria in epithelial ovarian carcinoma exhibit abnormal phenotypes and blunted associations with biobehavioral factors.
Authors: Bindra S. , McGill M.A. , Triplett M.K. , Tyagi A. , Thaker P.H. , Dahmoush L. , Goodheart M.J. , Ogden R.T. , Owusu-Ansah E. , R Karan K. , et al. .
Source: Scientific reports, 2021-06-02; 11(1), p. 11595.
EPub date: 2021-06-02.
PMID: 34078919
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Positive Psychosocial Factors and Oxytocin in the Ovarian Tumor Microenvironment.
Authors: Cuneo M.G. , Szeto A. , Schrepf A. , Thaker P.H. , Goodheart M. , Cole S.W. , Sood A.K. , McCabe P.M. , Mendez A.J. , Lutgendorf S.K. .
Source: Psychosomatic medicine, 2021-06-01; 83(5), p. 417-422.
PMID: 34080583
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Chronic difficulties are associated with poorer psychosocial functioning in the first year post-diagnosis in epithelial ovarian cancer patients.
Authors: Garvin L. , Slavich G.M. , Schrepf A. , Davis L.Z. , Thaker P.H. , Goodheart M.J. , Cole S.W. , Sood A.K. , Lutgendorf S.K. .
Source: Psycho-oncology, 2021 06; 30(6), p. 954-961.
EPub date: 2021-04-01.
PMID: 33760306
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Epithelial-mesenchymal transition polarization in ovarian carcinomas from patients with high social isolation.
Authors: Lutgendorf S.K. , Penedo F. , Goodheart M.J. , Dahmoush L. , Arevalo J.M.G. , Thaker P.H. , Slavich G.M. , Sood A.K. , Cole S.W. .
Source: Cancer, 2020-10-01; 126(19), p. 4407-4413.
EPub date: 2020-07-21.
PMID: 32691853
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Oxytocin in the tumor microenvironment is associated with lower inflammation and longer survival in advanced epithelial ovarian cancer patients.
Authors: Cuneo M.G. , Szeto A. , Schrepf A. , Kinner E.M. , Schachner B.I. , Ahmed R. , Thaker P.H. , Goodheart M. , Bender D. , Cole S.W. , et al. .
Source: Psychoneuroendocrinology, 2019 08; 106, p. 244-251.
EPub date: 2019-04-06.
PMID: 31005045
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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
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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 08; 124(16), p. 3401-3408.
EPub date: 2018-06-15.
PMID: 29905941
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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