{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:47:32Z","timestamp":1783655252438,"version":"3.55.0"},"reference-count":163,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T00:00:00Z","timestamp":1590710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ensign Endowment for Gynecologic Cancer Research","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA217685"],"award-info":[{"award-number":["CA217685"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013028","name":"Frank McGraw Memorial Chair in Cancer Research","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100013028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Non-epithelial ovarian tumors are heterogeneous and account for approximately 10% of ovarian malignancies. The most common subtypes of non-epithelial ovarian tumors arise from germ cells or sex cord and stromal cells of the gonads. These tumors are usually detected at an early stage, and management includes surgical staging and debulking. When indicated for advanced disease, most respond to chemotherapy; however, options for patients with refractory disease are limited, and regimens can be associated with significant toxicities, including permanent organ dysfunction, secondary malignancies, and death. Targeted therapies that potentially decrease chemotherapy-related adverse effects and improve outcomes for patients with chemotherapy-refractory disease are needed. Here, we review the molecular landscape of non-epithelial ovarian tumors for the purpose of informing rational clinical trial design. Recent genomic discoveries have uncovered recurring somatic alterations and germline mutations in subtypes of non-epithelial ovarian tumors. Though there is a paucity of efficacy data on targeted therapies, such as kinase inhibitors, antibody\u2013drug conjugates, immunotherapy, and hormonal therapy, exceptional responses to some compounds have been reported. The rarity and complexity of non-epithelial ovarian tumors warrant collaboration and efficient clinical trial design, including high-quality molecular characterization, to guide future efforts.<\/jats:p>","DOI":"10.3390\/cancers12061398","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T09:19:27Z","timestamp":1591089567000},"page":"1398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Molecular Pathways and Targeted Therapies for Malignant Ovarian Germ Cell Tumors and Sex Cord\u2013Stromal Tumors: A Contemporary Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7502-3923","authenticated-orcid":false,"given":"Asaf","family":"Maoz","sequence":"first","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-8701","authenticated-orcid":false,"given":"Koji","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5207-5109","authenticated-orcid":false,"given":"Marcia A.","family":"Ciccone","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-9994","authenticated-orcid":false,"given":"Shinya","family":"Matsuzaki","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6355-2820","authenticated-orcid":false,"given":"Maximilian","family":"Klar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Freiburg, 76100 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6960-4414","authenticated-orcid":false,"given":"Lynda D.","family":"Roman","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA 90033, USA"},{"name":"Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4242-1762","authenticated-orcid":false,"given":"Anil K.","family":"Sood","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9712-2140","authenticated-orcid":false,"given":"David M.","family":"Gershenson","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"ref_1","unstructured":"Serov, S.F., Scully, R.E., and Sobin, L.J. (1973). Histological typing of ovarian tumors in World Health Organization. Proceedings of International Histological Classification of Tumors, Geneva, Switzerland, The World Health Organization."},{"key":"ref_2","unstructured":"Kurman, R., Carcangiu, M., Herrington, C., and Young, R. (2014). World Health Organization Classification of Tumours of Female Reproductive Organs, The World Health Organization. [4th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3322\/caac.21456","article-title":"Ovarian cancer statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Testa, U., Petrucci, E., Pasquini, L., Castelli, G., and Pelosi, E. (2018). Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells. Medicines (Basel), 5.","DOI":"10.3390\/medicines5010016"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ygyno.2016.10.019","article-title":"The histology of ovarian cancer: Worldwide distribution and implications for international survival comparisons (CONCORD-2)","volume":"144","author":"Matz","year":"2017","journal-title":"Gynecol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1200\/JOP.2016.016261","article-title":"Ovarian Sex Cord-Stromal Tumors","volume":"12","author":"Schultz","year":"2016","journal-title":"J. Oncol. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2938","DOI":"10.1200\/JCO.2007.10.8738","article-title":"Management of ovarian germ cell tumors","volume":"25","author":"Gershenson","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1200\/JCO.2007.11.1005","article-title":"Management of ovarian stromal cell tumors","volume":"25","author":"Colombo","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1097\/SLA.0b013e31818447cd","article-title":"Comprehensive staging allows for excellent outcome in patients with localized malignant germ cell tumor of the ovary","volume":"248","author":"Palenzuela","year":"2008","journal-title":"Ann. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/1477-7819-9-123","article-title":"Residual tumor after the salvage surgery is the major risk factors for primary treatment failure in malignant ovarian germ cell tumors: A retrospective study of single institution","volume":"9","author":"Lee","year":"2011","journal-title":"World J. Surg. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/annonc\/mdw563","article-title":"The role of staging and adjuvant chemotherapy in stage I malignant ovarian germ cell tumors (MOGTs): The MITO-9 study","volume":"28","author":"Mangili","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_12","unstructured":"Bristow, R.E., Karlan, B.Y., and Chi, D.S. (2015). Surgery for Ovarian Cancer, CRC Press."},{"key":"ref_13","first-page":"iv1","article-title":"Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"29","author":"Morice","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.jpedsurg.2003.11.027","article-title":"Outcome and staging evaluation in malignant germ cell tumors of the ovary in children and adolescents: An intergroup study","volume":"39","author":"Billmire","year":"2004","journal-title":"J. Pediatr. Surg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.ygyno.2013.08.016","article-title":"The significance of comprehensive staging surgery in malignant ovarian germ cell tumors","volume":"131","author":"Liu","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_16","first-page":"268","article-title":"Current therapy for dysgerminoma of the ovary","volume":"70","author":"Thomas","year":"1987","journal-title":"Obstet. Gynecol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.ygyno.2011.01.006","article-title":"Is surgical restaging indicated in apparent stage IA pure ovarian dysgerminoma? The MITO group retrospective experience","volume":"121","author":"Mangili","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.ygyno.2018.11.032","article-title":"Ovarian function, fertility, and menopause occurrence after fertility-sparing surgery and chemotherapy for ovarian neoplasms","volume":"152","author":"Ceppi","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/IGC.0000000000000358","article-title":"Management of bilateral malignant ovarian germ cell tumors: A MITO-9 retrospective study","volume":"25","author":"Sigismondi","year":"2015","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3109\/00016340903348383","article-title":"Young girls with malignant ovarian germ cell tumors can undergo normal menarche and menstruation after fertility-preserving surgery and adjuvant chemotherapy","volume":"89","author":"Yoo","year":"2010","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1479-828X.1999.tb03382.x","article-title":"Fertility and ovarian function after conservative surgery for germ cell tumours of the ovary","volume":"39","author":"Perrin","year":"1999","journal-title":"Aust. N. Z. J. Obstet. Gynaecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/jso.21079","article-title":"The influence of conservative surgical practices for malignant ovarian germ cell tumors","volume":"98","author":"Chan","year":"2008","journal-title":"J. Surg. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ygyno.2008.12.007","article-title":"Patterns of metastasis in sex cord-stromal tumors of the ovary: Can routine staging lymphadenectomy be omitted?","volume":"113","author":"Brown","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/bjc.2011.267","article-title":"Prognostic impact of lymphadenectomy in clinically early stage malignant germ cell tumour of the ovary","volume":"105","author":"Mahdi","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ygyno.2017.10.022","article-title":"Prognostic significance of lymphadenectomyin malignant ovarian sex cord stromal tumor: A retrospective cohort study and meta-analysis","volume":"148","author":"Cheng","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/IGC.0000000000000659","article-title":"Prognostic Factors in Adult Granulosa Cell Tumor: A Long Follow-Up at a Single Center","volume":"26","author":"Karalok","year":"2016","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejogrb.2017.10.010","article-title":"Retroperitoneal nodal metastasis in primary adult type granulosa cell tumor of the ovary: Can routine lymphadenectomy be omitted?","volume":"219","author":"Kuru","year":"2017","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/jog.13928","article-title":"Does lymphadenectomy effect postoperative surgical morbidity and survival in patients with adult granulosa cell tumor of ovary?","volume":"45","author":"Erkilinc","year":"2019","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"vii20","DOI":"10.1093\/annonc\/mds223","article-title":"Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"23","author":"Colombo","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"De Giorgi, U., Casadei, C., Bergamini, A., Attademo, L., Cormio, G., Lorusso, D., Pignata, S., and Mangili, G. (2019). Therapeutic Challenges for Cisplatin-Resistant Ovarian Germ Cell Tumors. Cancers (Basel), 11.","DOI":"10.3390\/cancers11101584"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1093\/annonc\/mdw662","article-title":"Fifth Ovarian Cancer Consensus Conference of the Gynecologic Cancer InterGroup (GCIG): Clinical trial design for rare ovarian tumours","volume":"28","author":"Leary","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1093\/annonc\/mdx259","article-title":"Salvage high-dose chemotherapy in female patients with relapsed\/refractory germ-cell tumors: A retrospective analysis of the European Group for Blood and Marrow Transplantation (EBMT)","volume":"28","author":"Richard","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1200\/JCO.2014.59.4325","article-title":"High-dose chemotherapy for recurrent ovarian germ cell tumors","volume":"33","author":"Matei","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.ygyno.2019.06.025","article-title":"Global incidence comparisons and trends in ovarian germ cell tumors by geographic region in girls, adolescents and young women: 1988\u20132012","volume":"154","author":"Hubbard","year":"2019","journal-title":"Gynecol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.ygyno.2009.05.039","article-title":"Racial disparities in survival among patients with germ cell tumors of the ovary\u2013United States","volume":"114","author":"Bryant","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1097\/01.AOG.0000216004.22588.ce","article-title":"Incidence and survival rates for female malignant germ cell tumors","volume":"107","author":"Smith","year":"2006","journal-title":"Obstet. Gynecol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1210\/er.2012-1045","article-title":"Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: Implications for pathogenesis","volume":"34","author":"Kraggerud","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ygyno.2013.08.028","article-title":"Malignant ovarian germ cell tumors: Presentation, survival and second cancer in a population based Norwegian cohort (1953\u20132009)","volume":"131","author":"Solheim","year":"2013","journal-title":"Gynecol. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1097\/COC.0b013e3181841f2e","article-title":"Malignant ovarian germ cell tumors: A single-institution experience","volume":"32","author":"Cicin","year":"2009","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/cge.12917","article-title":"Genetics and genomics of ovarian sex cord-stromal tumors","volume":"91","author":"Fuller","year":"2017","journal-title":"Clin. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1586\/14737140.2013.811174","article-title":"Genetic changes in nonepithelial ovarian cancer","volume":"13","author":"Lambrechts","year":"2013","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ygyno.2018.08.013","article-title":"The genetic landscape of 87 ovarian germ cell tumors","volume":"151","author":"Busschaert","year":"2018","journal-title":"Gynecol. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0029-7844(95)00192-T","article-title":"Surgical management of malignant ovarian germ-cell tumors: 10 years\u2019 experience of 129 patients","volume":"86","author":"Peccatori","year":"1995","journal-title":"Obstet. Gynecol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0046-8177(77)80115-9","article-title":"Malignant germ cell tumors of the ovary","volume":"8","author":"Kurman","year":"1977","journal-title":"Hum. Pathol."},{"key":"ref_45","unstructured":"Barakat, R.R.B., Berchuck, A., Markman, M., and Randall, M.E. (2013). Principles and Practice of Gynecologic Oncology, Lippincott Williams & Wilkins. [6th ed.]."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejca.2019.03.001","article-title":"A multicentre retrospective cohort study of ovarian germ cell tumours: Evidence for chemotherapy de-escalation and alignment of paediatric and adult practice","volume":"113","author":"Newton","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1200\/JCO.1994.12.4.701","article-title":"Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: A trial of the Gynecologic Oncology Group","volume":"12","author":"Williams","year":"1994","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1200\/JCO.1990.8.4.715","article-title":"Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin","volume":"8","author":"Gershenson","year":"1990","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1093\/annonc\/mdx360","article-title":"Long-term toxicity of cisplatin in germ-cell tumor survivors","volume":"28","author":"Chovanec","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejca.2017.11.030","article-title":"Paediatric dysgerminoma: Results of three consecutive French germ cell tumours clinical studies (TGM-85\/90\/95) with late effects study","volume":"91","author":"Pacquement","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1093\/annonc\/mdn162","article-title":"Survival and reproductive function of 52 women treated with surgery and bleomycin, etoposide, cisplatin (BEP) chemotherapy for ovarian yolk sac tumor","volume":"19","author":"Pautier","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1200\/JCO.2006.08.4590","article-title":"Reproductive and sexual function after platinum-based chemotherapy in long-term ovarian germ cell tumor survivors: A Gynecologic Oncology Group Study","volume":"25","author":"Gershenson","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ygyno.2004.07.044","article-title":"Adjuvant therapy of completely resected dysgerminoma with carboplatin and etoposide: A trial of the Gynecologic Oncology Group","volume":"95","author":"Williams","year":"2004","journal-title":"Gynecol. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/oxfordjournals.annonc.a010493","article-title":"A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with \u2018good-risk\u2019 metastatic non-seminomatous germ cell tumors","volume":"7","author":"Bokemeyer","year":"1996","journal-title":"Ann. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/cncr.29732","article-title":"Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative","volume":"122","author":"Pashankar","year":"2016","journal-title":"Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Heskett, M.B., Sanborn, J.Z., Boniface, C., Goode, B., Chapman, J., Garg, K., Rabban, J.T., Zaloudek, C., Benz, S.C., and Spellman, P.T. (2020). Multiregion exome sequencing of ovarian immature teratomas reveals 2N near-diploid genomes, paucity of somatic mutations, and extensive allelic imbalances shared across mature, immature, and disseminated components. Mod. Pathol.","DOI":"10.1101\/818534"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/GCO.0000000000000340","article-title":"Pathogenesis and heterogeneity of ovarian cancer","volume":"29","author":"Kroeger","year":"2017","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1016\/j.celrep.2018.05.039","article-title":"Integrated Molecular Characterization of Testicular Germ Cell Tumors","volume":"23","author":"Shen","year":"2018","journal-title":"Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"AACR Project GENIE Consortium (2017). AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discov., 7, 818\u2013831.","DOI":"10.1158\/2159-8290.CD-17-0151"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"607","DOI":"10.3109\/08820139509066861","article-title":"Accumulation of gamma\/delta T cells in human dysgerminoma and seminoma: Roles in autologous tumor killing and granuloma formation","volume":"24","author":"Zhao","year":"1995","journal-title":"Immunol. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.1002\/1097-0142(19930415)71:8<2562::AID-CNCR2820710821>3.0.CO;2-E","article-title":"Dysgerminoma of the ovary. An immunohistochemical study of tumor-infiltrating lymphoreticular cells and tumor cells","volume":"71","author":"Dietl","year":"1993","journal-title":"Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/j.1365-2559.1992.tb01033.x","article-title":"Characterization of the inflammatory infiltrate in ovarian dysgerminoma: An immunocytochemical study","volume":"20","author":"Stewart","year":"1992","journal-title":"Histopathology"},{"key":"ref_64","first-page":"2201","article-title":"Immunohistologic characterization of lymphoid cells infiltrating dysgerminoma of the ovary","volume":"38","author":"Honma","year":"1986","journal-title":"Nihon Sanka Fujinka Gakkai Zasshi"},{"key":"ref_65","first-page":"1013","article-title":"The significance of lymphocytic infiltration for the prognosis in dysgerminomas","volume":"110","author":"Steffen","year":"1980","journal-title":"Schweiz. Med. Wochenschr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.4049\/jimmunol.0803424","article-title":"The microenvironment of germ cell tumors harbors a prominent antigen-driven humoral response","volume":"182","author":"Willis","year":"2009","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3389\/fimmu.2015.00067","article-title":"Tertiary Lymphoid Structure-Associated B Cells are Key Players in Anti-Tumor Immunity","volume":"6","author":"Germain","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.it.2014.09.006","article-title":"Tertiary lymphoid structures in cancer and beyond","volume":"35","author":"Goc","year":"2014","journal-title":"Trends Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.3389\/fimmu.2019.01884","article-title":"The Crohn\u2019s-Like Lymphoid Reaction to Colorectal Cancer-Tertiary Lymphoid Structures with Immunologic and Potentially Therapeutic Relevance in Colorectal Cancer","volume":"10","author":"Maoz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e1305535","DOI":"10.1080\/2162402X.2017.1305535","article-title":"Deep exploration of the immune infiltrate and outcome prediction in testicular cancer by quantitative multiplexed immunohistochemistry and gene expression profiling","volume":"6","author":"Siska","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/bjc.2015.244","article-title":"Frequent PD-L1 expression in testicular germ cell tumors","volume":"113","author":"Fankhauser","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/his.14016","article-title":"Ovarian germ cell tumour classification: Views from the testis","volume":"76","author":"Berney","year":"2020","journal-title":"Histopathology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.ygyno.2014.05.003","article-title":"Malignant ovarian germ cell tumor\u2014Role of surgical staging and gonadal dysgenesis","volume":"134","author":"Lin","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1002\/1097-0142(197006)25:6<1340::AID-CNCR2820250612>3.0.CO;2-N","article-title":"Gonadoblastoma. A review of 74 cases","volume":"25","author":"Scully","year":"1970","journal-title":"Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1159\/000314536","article-title":"Tumor risk in disorders of sex development","volume":"4","author":"Pleskacova","year":"2010","journal-title":"Sex. Dev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2096","DOI":"10.1002\/cncr.25794","article-title":"KIT gene mutation and amplification in dysgerminoma of the ovary","volume":"117","author":"Cheng","year":"2011","journal-title":"Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s12079-017-0399-1","article-title":"The stem cell factor (SCF)\/c-KIT signalling in testis and prostate cancer","volume":"11","author":"Cardoso","year":"2017","journal-title":"J. Cell Commun. Signal."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.1200\/JCO.2003.04.190","article-title":"Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor","volume":"21","author":"Heinrich","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/modpathol.3800576","article-title":"Chromosome 12p abnormalities in dysgerminoma of the ovary: A FISH analysis","volume":"19","author":"Zhang","year":"2006","journal-title":"Mod. Pathol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1158\/1078-0432.CCR-14-2662","article-title":"KRAS as a Therapeutic Target","volume":"21","author":"McCormick","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Maoz, A., Ciccone, M.A., Matsuzaki, S., Coleman, R.L., and Matsuo, K. (2019). Emerging serine-threonine kinase inhibitors for treating ovarian cancer. Expert Opin. Emerg. Drugs.","DOI":"10.1080\/14728214.2019.1696773"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ygyno.2012.03.019","article-title":"Current advances in the management of malignant germ cell and sex cord-stromal tumors of the ovary","volume":"125","author":"Gershenson","year":"2012","journal-title":"Gynecol. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1200\/JCO.18.02419","article-title":"Management of Rare Ovarian Cancer Histologies","volume":"37","author":"Gershenson","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1080\/13543784.2016.1181748","article-title":"Clinical outcome of treatment with serine-threonine kinase inhibitors in recurrent epithelial ovarian cancer: A systematic review of literature","volume":"25","author":"Ciccone","year":"2016","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.ygyno.2015.02.003","article-title":"The PI3K\/AKT\/mTOR pathway as a therapeutic target in ovarian cancer","volume":"137","author":"Mabuchi","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ctrv.2017.11.002","article-title":"Targeting the Wnt\/beta-catenin pathway in cancer: Update on effectors and inhibitors","volume":"62","author":"Krishnamurthy","year":"2018","journal-title":"Cancer Treat. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.ygyno.2005.02.007","article-title":"Ovarian cancer incidence in the United States, 1992\u20131999","volume":"97","author":"Quirk","year":"2005","journal-title":"Gynecol. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/his.12052","article-title":"A practical approach to immunohistochemical diagnosis of ovarian germ cell tumours and sex cord-stromal tumours","volume":"62","author":"Rabban","year":"2013","journal-title":"Histopathology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.humpath.2006.01.019","article-title":"OCT4 is superior to CD30 in the diagnosis of metastatic embryonal carcinomas after chemotherapy","volume":"37","author":"Sung","year":"2006","journal-title":"Hum. Pathol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1177\/002215540205000216","article-title":"CD30 and CD117 (c-kit) used in combination are useful for distinguishing embryonal carcinoma from seminoma","volume":"50","author":"Leroy","year":"2002","journal-title":"J. Histochem. Cytochem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1200\/JCO.2004.12.074","article-title":"The Activity of Taxanes in the Treatment of Sex Cord-Stromal Ovarian Tumors","volume":"22","author":"Brown","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ygyno.2011.03.020","article-title":"Patterns of spread and recurrence of sex cord-stromal tumors of the ovary","volume":"122","author":"Thrall","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.ygyno.2006.08.032","article-title":"Prognostic factors responsible for survival in sex cord stromal tumors of the ovary\u2013An analysis of 376 women","volume":"104","author":"Zhang","year":"2007","journal-title":"Gynecol. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1056\/NEJMoa0902542","article-title":"Mutation of FOXL2 in granulosa-cell tumors of the ovary","volume":"360","author":"Shah","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00292-018-0562-3","article-title":"Sex cord-stromal tumors of the ovary: Current aspects with a focus on granulosa cell tumors, Sertoli-Leydig cell tumors, and gynandroblastomas","volume":"40","author":"Kommoss","year":"2019","journal-title":"Pathologe"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/1097-0142(197501)35:1<231::AID-CNCR2820350128>3.0.CO;2-O","article-title":"A clinicopathologic study of 92 cases of granulosa cell tumor of the ovary with special reference to the factors influencing prognosis","volume":"35","author":"Fox","year":"1975","journal-title":"Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/0090-8258(83)90083-5","article-title":"Granulosa cell tumors in Israel: A study of 172 cases","volume":"15","author":"Ohel","year":"1983","journal-title":"Gynecol. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Yanagida, S., Anglesio, M.S., Nazeran, T.M., Lum, A., Inoue, M., Iida, Y., Takano, H., Nikaido, T., Okamoto, A., and Huntsman, D.G. (2017). Clinical and genetic analysis of recurrent adult-type granulosa cell tumor of the ovary: Persistent preservation of heterozygous c.402C > G FOXL2 mutation. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0178989"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/PAS.0000000000001232","article-title":"DICER1 and FOXL2 Mutation Status Correlates with Clinicopathologic Features in Ovarian Sertoli-Leydig Cell Tumors","volume":"43","author":"Karnezis","year":"2019","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/modpathol.2012.226","article-title":"FOXL2 molecular testing in ovarian neoplasms: Diagnostic approach and procedural guidelines","volume":"26","author":"Kommoss","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/modpathol.2010.145","article-title":"The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary","volume":"23","author":"Jamieson","year":"2010","journal-title":"Mod. Pathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.biocel.2016.01.003","article-title":"Impact of FOXL2 mutations on signaling in ovarian granulosa cell tumors","volume":"72","author":"Leung","year":"2016","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e04207","DOI":"10.7554\/eLife.04207","article-title":"The transcription factor FOXL2 mobilizes estrogen signaling to maintain the identity of ovarian granulosa cells","volume":"3","author":"Georges","year":"2014","journal-title":"eLife"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1038\/onc.2012.298","article-title":"Adult ovarian granulosa cell tumor transcriptomics: Prevalence of FOXL2 target genes misregulation gives insights into the pathogenic mechanism of the p.Cys134Trp somatic mutation","volume":"32","author":"Benayoun","year":"2013","journal-title":"Oncogene"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/his.13978","article-title":"Practical roles for molecular diagnostic testing in ovarian adult granulosa cell tumour, Sertoli-Leydig cell tumour, microcystic stromal tumour and their mimics","volume":"76","author":"Rabban","year":"2020","journal-title":"Histopathology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1210\/me.2009-0375","article-title":"FOXL2 interacts with steroidogenic factor-1 (SF-1) and represses SF-1-induced CYP17 transcription in granulosa cells","volume":"24","author":"Park","year":"2010","journal-title":"Mol. Endocrinol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Fleming, N.I., Knower, K.C., Lazarus, K.A., Fuller, P.J., Simpson, E.R., and Clyne, C.D. (2010). Aromatase is a direct target of FOXL2: C134W in granulosa cell tumors via a single highly conserved binding site in the ovarian specific promoter. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014389"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1158\/1541-7786.MCR-18-0359","article-title":"Mutational Landscape of Ovarian Adult Granulosa Cell Tumors from Whole Exome and Targeted TERT Promoter Sequencing","volume":"17","author":"Alexiadis","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s41379-018-0007-9","article-title":"TERT promoter mutation in adult granulosa cell tumor of the ovary","volume":"31","author":"Pilsworth","year":"2018","journal-title":"Mod. Pathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1038\/ng.3849","article-title":"Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes","volume":"49","author":"Wang","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1097\/01.MP.0000024290.55261.14","article-title":"Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors","volume":"15","author":"Mayr","year":"2002","journal-title":"Mod. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Caburet, S., Anttonen, M., Todeschini, A.L., Unkila-Kallio, L., Mestivier, D., Butzow, R., and Veitia, R.A. (2015). Combined comparative genomic hybridization and transcriptomic analyses of ovarian granulosa cell tumors point to novel candidate driver genes. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1283-0"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1210\/jc.2005-2710","article-title":"Activating mutations of the stimulatory g protein in juvenile ovarian granulosa cell tumors: A new prognostic factor?","volume":"91","author":"Kalfa","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ebiom.2015.03.002","article-title":"A Hot-spot of In-frame Duplications Activates the Oncoprotein AKT1 in Juvenile Granulosa Cell Tumors","volume":"2","author":"Bessiere","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.cellsig.2006.02.011","article-title":"FSH signaling pathways in immature granulosa cells that regulate target gene expression: Branching out from protein kinase A","volume":"18","author":"Maizels","year":"2006","journal-title":"Cell Signal."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1530\/EJE-10-0849","article-title":"Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are highly expressed in ovarian granulosa cell tumors","volume":"164","author":"Farkkila","year":"2011","journal-title":"Eur. J. Endocrinol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"E1973","DOI":"10.1210\/jc.2011-1812","article-title":"Serum vascular endothelial growth factor A (VEGF) is elevated in patients with ovarian granulosa cell tumor (GCT), and VEGF inhibition by bevacizumab induces apoptosis in GCT in vitro","volume":"96","author":"Farkkila","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ejogrb.2008.02.009","article-title":"Glucose metabolism and angiogenesis in granulosa cell tumors of the ovary: Activation of Akt, expression of M2PK, TKTL1 and VEGF","volume":"139","author":"Schmidt","year":"2008","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1177\/1933719108317584","article-title":"Expression of c-kit and platelet-derived growth factor receptors in ovarian granulosa cell tumors","volume":"15","author":"Rocconi","year":"2008","journal-title":"Reprod. Sci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1056\/NEJMoa1102903","article-title":"Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers","volume":"366","author":"Anglesio","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1097\/PAS.0000000000000895","article-title":"DICER1 Mutations Are Consistently Present in Moderately and Poorly Differentiated Sertoli-Leydig Cell Tumors","volume":"41","author":"Terzic","year":"2017","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.ygyno.2011.03.024","article-title":"Ovarian sex cord-stromal tumors, pleuropulmonary blastoma and DICER1 mutations: A report from the International Pleuropulmonary Blastoma Registry","volume":"122","author":"Schultz","year":"2011","journal-title":"Gynecol. Oncol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/his.12747","article-title":"DICER1 and FOXL2 mutations in ovarian sex cord-stromal tumours: A GINECO Group study","volume":"68","author":"Goulvent","year":"2016","journal-title":"Histopathology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1002\/1097-0142(19821001)50:7<1384::AID-CNCR2820500726>3.0.CO;2-5","article-title":"Ovarian sex cord tumor with annular tubules: Review of 74 cases including 27 with Peutz-Jeghers syndrome and four with adenoma malignum of the cervix","volume":"50","author":"Young","year":"1982","journal-title":"Cancer"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrc.2015.18","article-title":"The kinome \u2018at large\u2019 in cancer","volume":"16","author":"Fleuren","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1111\/j.1447-0756.2011.01649.x","article-title":"Third-line chemotherapy with tyrosine kinase inhibitor (imatinib mesylate) in recurrent ovarian granulosa cell tumor: Case report","volume":"37","author":"Raspagliesi","year":"2011","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"a003434","DOI":"10.1101\/mcs.a003434","article-title":"Personalized prescription of imatinib in recurrent granulosa cell tumor of the ovary: Case report","volume":"5","author":"Poddubskaya","year":"2019","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s10637-009-9280-2","article-title":"Phase II trial of sunitinib in patients with relapsed or refractory germ cell tumors","volume":"28","author":"Feldman","year":"2010","journal-title":"Investig. New Drugs"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/S1470-2045(09)70368-7","article-title":"Targeted therapies for rare gynaecological cancers","volume":"11","author":"Manchana","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/cncr.28421","article-title":"Efficacy and safety of bevacizumab in recurrent sex cord-stromal ovarian tumors: Results of a phase 2 trial of the Gynecologic Oncology Group","volume":"120","author":"Brown","year":"2014","journal-title":"Cancer"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ygyno.2009.04.021","article-title":"Anti-angiogenesis therapy with bevacizumab for patients with ovarian granulosa cell tumors","volume":"114","author":"Tao","year":"2009","journal-title":"Gynecol. Oncol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"viii333","DOI":"10.1093\/annonc\/mdy285.143","article-title":"Alienor\/ENGOT-ov7 randomized trial exploring weekly paclitaxel (wP) + bevacizumab (bev) vs. wP alone for patients with ovarian sex cord tumors (SCT) in relapse","volume":"29","author":"Harter","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1373\/clinchem.2019.303644","article-title":"Biomarkers for Predicting Response to Immunotherapy with Immune Checkpoint Inhibitors in Cancer Patients","volume":"65","author":"Duffy","year":"2019","journal-title":"Clin. Chem."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","article-title":"The Immune Landscape of Cancer","volume":"48","author":"Thorsson","year":"2018","journal-title":"Immunity"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ygyno.2015.01.514","article-title":"PD-1 and PD-L1 expression in 1599 gynecological malignancies-implications for immunotherapy","volume":"137","author":"Herzog","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/annonc\/mdx680","article-title":"Phase II trial of pembrolizumab in patients with platinum refractory germ-cell tumors: A Hoosier Cancer Research Network Study GU14-206","volume":"29","author":"Adra","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"e11","DOI":"10.1056\/NEJMc1616637","article-title":"T-Cell Transfer Therapy Targeting Mutant KRAS","volume":"376","author":"Rosenberg","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1158\/2326-6066.CIR-18-0065","article-title":"CD30-Redirected Chimeric Antigen Receptor T Cells Target CD30(+) and CD30(-) Embryonal Carcinoma via Antigen-Dependent and Fas\/FasL Interactions","volume":"6","author":"Hong","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1111\/aogs.12720","article-title":"Evaluation of response to hormone therapy in patients with measurable adult granulosa cell tumors of the ovary","volume":"94","author":"Buist","year":"2015","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_140","first-page":"393","article-title":"Leuprolide acetate for treating refractory or persistent ovarian granulosa cell tumor","volume":"41","author":"Fishman","year":"1996","journal-title":"J. Reprod. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.ygyno.2006.06.022","article-title":"Anastrozole therapy in recurrent ovarian adult granulosa cell tumors: A report of 2 cases","volume":"103","author":"Freeman","year":"2006","journal-title":"Gynecol. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ygyno.2014.03.573","article-title":"Hormone therapy in ovarian granulosa cell tumors: A systematic review","volume":"134","author":"Limpens","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"IJE08","DOI":"10.2217\/ije-2017-0021","article-title":"Ovarian adult-type granulosa cell tumor: Focusing on endocrine-based therapies","volume":"5","author":"Yang","year":"2018","journal-title":"Int. J. Endocr. Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"5524","DOI":"10.1200\/JCO.2018.36.15_suppl.5524","article-title":"PARAGON: A phase 2 study of anastrozole (An) in patients with estrogen receptor(ER) and\/progesterone receptor (PR) positive recurrent\/metastatic granulosa cell tumors\/sex-cord stromal tumors (GCT) of the ovary","volume":"36","author":"Banerjee","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e165","DOI":"10.1200\/JCO.2012.45.0346","article-title":"Cytochrome P17 inhibition with ketoconazole as treatment for advanced granulosa cell ovarian tumor","volume":"31","author":"Hurtado","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Garcia-Donas, J., Hurtado, A., Garrigos, L., Santaballa, A., Redondo, A., Vidal, L., Lainez, N., Guerra, E., Rodriguez, V., and Cueva, J. (2019, April 24). Open Label Phase III Clinical Trial of Ketoconazole as CYP17 Inhibitor in Metastatic or Advanced Non-Resectable Granulosa Cell Ovarian Tumors. The GREKO (GRanulosa Et KetOconazole) Trial. GETHI 2011-03. Available online: https:\/\/ssrn.com\/abstract=3377550.","DOI":"10.2139\/ssrn.3377550"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1200\/JCO.2017.35.15_suppl.5577","article-title":"Open label phase II clinical trial of orteronel (TAK-700) in metastatic or advanced non-resectable granulosa cell ovarian tumors: The Greko II study","volume":"35","author":"Garrigos","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev-pharmtox-010818-021649","article-title":"New Cell Cycle Inhibitors Target Aneuploidy in Cancer Therapy","volume":"59","author":"Kawakami","year":"2019","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/01.coc.0000195086.47548.ef","article-title":"Phase II study of imatinib mesylate in chemotherapy refractory germ cell tumors expressing KIT","volume":"29","author":"Einhorn","year":"2006","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/S1470-2045(07)70344-3","article-title":"Complete response after treatment with imatinib in pretreated disseminated testicular seminoma with overexpression of c-KIT","volume":"8","author":"Pedersini","year":"2007","journal-title":"Lancet Oncol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1093\/annonc\/mdx124","article-title":"Pazopanib in advanced germ cell tumors after chemotherapy failure: Results of the open-label, single-arm, phase 2 Pazotest trial","volume":"28","author":"Necchi","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s13045-014-0052-x","article-title":"Next generation sequencing analysis of platinum refractory advanced germ cell tumor sensitive to Sunitinib (Sutent(R)) a VEGFR2\/PDGFRbeta\/c-kit\/ FLT3\/RET\/CSF1R inhibitor in a phase II trial","volume":"7","author":"Subbiah","year":"2014","journal-title":"J. Hematol. Oncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/COC.0b013e31827de90d","article-title":"Phase II clinical trial of oxaliplatin and bevacizumab in refractory germ cell tumors","volume":"37","author":"Jain","year":"2014","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1007\/s10637-013-9934-y","article-title":"A phase 2 multicenter study of tivantinib (ARQ 197) monotherapy in patients with relapsed or refractory germ cell tumors","volume":"31","author":"Feldman","year":"2013","journal-title":"Investig. New Drugs"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1007\/s00432-018-2752-z","article-title":"Everolimus in patients with multiply relapsed or cisplatin refractory germ cell tumors: Results of a phase II, single-arm, open-label multicenter trial (RADIT) of the German Testicular Cancer Study Group","volume":"145","author":"Fenner","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/s10637-019-00805-4","article-title":"Phase II study of avelumab in multiple relapsed\/refractory germ cell cancer","volume":"37","author":"Mego","year":"2019","journal-title":"Investig. New Drugs"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1634\/theoncologist.2017-0544","article-title":"Treatment of CD30-Expressing Germ Cell Tumors and Sex Cord Stromal Tumors with Brentuximab Vedotin: Identification and Report of Seven Cases","volume":"23","author":"Albany","year":"2018","journal-title":"Oncologist"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"eaaw8412","DOI":"10.1126\/scitranslmed.aaw8412","article-title":"Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials","volume":"11","author":"Lin","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/nature20596","article-title":"Genomic evolution and chemoresistance in germ-cell tumours","volume":"540","author":"Zack","year":"2016","journal-title":"Nature"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1126\/science.aaw3145","article-title":"The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice","volume":"364","author":"Engle","year":"2019","journal-title":"Science"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"4368","DOI":"10.1158\/1078-0432.CCR-08-0325","article-title":"Multi-arm clinical trials of new agents: Some design considerations","volume":"14","author":"Freidlin","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/s41591-019-0424-4","article-title":"Genomic and transcriptomic profiling expands precision cancer medicine: The WINTHER trial","volume":"25","author":"Rodon","year":"2019","journal-title":"Nat. Med."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13073-018-0529-2","article-title":"From somatic variants towards precision oncology: Evidence-driven reporting of treatment options in molecular tumor boards","volume":"10","author":"Hutter","year":"2018","journal-title":"Genome Med."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1398\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:33:48Z","timestamp":1760175228000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/6\/1398"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,29]]},"references-count":163,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["cancers12061398"],"URL":"https:\/\/doi.org\/10.3390\/cancers12061398","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,29]]}}}