Table of Contents Author Guidelines Submit a Manuscript
Sarcoma
Volume 2015, Article ID 243298, 14 pages
http://dx.doi.org/10.1155/2015/243298
Review Article

Potential Therapeutic Targets in Uterine Sarcomas

1Department of Oncology, Gynaecologic Oncology, KU Leuven (University of Leuven), 3000 Leuven, Belgium
2Department of Obstetrics and Gynaecology, University Hospitals Leuven, 3000 Leuven, Belgium
3Center for Gynaecologic Oncology Amsterdam (CGOA), Antoni van Leeuwenhoek-Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands

Received 14 August 2015; Accepted 30 September 2015

Academic Editor: Silvia Stacchiotti

Copyright © 2015 Tine Cuppens et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. V. M. Abeler, O. Røyne, S. Thoresen, H. E. Danielsen, J. M. Nesland, and G. B. Kristensen, “Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients,” Histopathology, vol. 54, no. 3, pp. 355–364, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. F. Amant, A. Coosemans, M. Debiec-Rychter, D. Timmerman, and I. Vergote, “Clinical management of uterine sarcomas,” The Lancet Oncology, vol. 10, no. 12, pp. 1188–1198, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Arenas, A. Rovirosa, V. Hernández et al., “Uterine sarcomas in breast cancer patients treated with tamoxifen,” International Journal of Gynecological Cancer, vol. 16, no. 2, pp. 861–865, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. A. S. Felix, L. S. Cook, M. M. Gaudet et al., “The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium,” British Journal of Cancer, vol. 108, no. 3, pp. 727–734, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. S. M. Schwartz, N. S. Weiss, J. R. Daling et al., “Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus,” Cancer, vol. 77, no. 4, pp. 717–724, 1996. View at Publisher · View at Google Scholar · View at Scopus
  6. R. Mancari, M. Signorelli, A. Gadducci et al., “Adjuvant chemotherapy in stage I-II uterine leiomyosarcoma: a multicentric retrospective study of 140 patients,” Gynecologic Oncology, vol. 133, no. 3, pp. 531–536, 2014. View at Publisher · View at Google Scholar · View at Scopus
  7. K. Lusby, K. B. Savannah, E. G. Demicco et al., “Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers: a single institution's experience,” Annals of Surgical Oncology, vol. 20, no. 7, pp. 2364–2372, 2013. View at Publisher · View at Google Scholar · View at Scopus
  8. F. Amant, D. Lorusso, A. Mustea, F. Duffaud, and P. Pautier, “Management strategies in advanced uterine leiomyosarcoma: focus on trabectedin,” Sarcoma, vol. 2015, Article ID 704124, 14 pages, 2015. View at Publisher · View at Google Scholar
  9. M. L. Hensley, R. Maki, E. Venkatraman et al., “Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial,” Journal of Clinical Oncology, vol. 20, no. 12, pp. 2824–2831, 2002. View at Publisher · View at Google Scholar · View at Scopus
  10. M. L. Hensley, J. A. Blessing, K. Degeest, O. Abulafia, P. G. Rose, and H. D. Homesley, “Fixed-dose rate gemcitabine plus docetaxel as second-line therapy for metastatic uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study,” Gynecologic Oncology, vol. 109, no. 3, pp. 323–328, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. D. M. Hyman, R. N. Grisham, and M. L. Hensley, “Management of advanced uterine leiomyosarcoma,” Current Opinion in Oncology, vol. 26, no. 4, pp. 422–427, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. G. D. Demetri, S. P. Chawla, M. von Mehren et al., “Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules,” Journal of Clinical Oncology, vol. 27, no. 25, pp. 4188–4196, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. B. J. Monk, J. A. Blessing, D. G. Street, C. Y. Muller, J. J. Burke, and M. L. Hensley, “A phase II evaluation of trabectedin in the treatment of advanced, persistent, or recurrent uterine leiomyosarcoma: a gynecologic oncology group study,” Gynecologic Oncology, vol. 124, no. 1, pp. 48–52, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. W. Kildal, V. M. Abeler, G. B. Kristensen, M. Jenstad, S. Ø. Thoresen, and H. E. Danielsen, “The prognostic value of DNA ploidy in a total population of uterine sarcomas,” Annals of Oncology, vol. 20, no. 6, pp. 1037–1041, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Raish, M. Khurshid, M. A. Ansari et al., “Analysis of molecular cytogenetic alterations in uterine leiomyosarcoma by array-based comparative genomic hybridization,” Journal of Cancer Research and Clinical Oncology, vol. 138, no. 7, pp. 1173–1186, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Murray, H. Linardou, G. Mountzios et al., “Low frequency of somatic mutations in uterine sarcomas: a molecular analysis and review of the literature,” Mutation Research, vol. 686, no. 1-2, pp. 68–73, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. T. P. Fleming, A. Saxena, W. C. Clark et al., “Amplification and/or overexpression of platelet-derived growth factor receptors and epidermal growth factor receptor in human glial tumors,” Cancer Research, vol. 52, no. 16, pp. 4550–4553, 1992. View at Google Scholar · View at Scopus
  18. M. C. Heinrich, C. L. Corless, G. D. Demetri et al., “Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor,” Journal of Clinical Oncology, vol. 21, no. 23, pp. 4342–4349, 2003. View at Publisher · View at Google Scholar · View at Scopus
  19. C. L. Sawyers, “Imatinib GIST keeps finding new indications: successful treatment of dermatofibrosarcoma protuberans by targeted inhibition of the platelet-derived growth factor receptor,” Journal of Clinical Oncology, vol. 20, no. 17, pp. 3568–3569, 2002. View at Google Scholar · View at Scopus
  20. Y. L. Cho, S. Bae, M. S. Koo et al., “Array comparative genomic hybridization analysis of uterine leiomyosarcoma,” Gynecologic Oncology, vol. 99, no. 3, pp. 545–551, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. S. F. Adams, J. A. Hickson, J. Y. Hutto, A. G. Montag, E. Lengyel, and S. D. Yamada, “PDGFR-α as a potential therapeutic target in uterine sarcomas,” Gynecologic Oncology, vol. 104, no. 3, pp. 524–528, 2007. View at Publisher · View at Google Scholar · View at Scopus
  22. J. J. Caudell, M. T. Deavers, B. M. Slomovitz et al., “Imatinib mesylate (gleevec)-targeted kinases are expressed in uterine sarcomas,” Applied Immunohistochemistry and Molecular Morphology, vol. 13, no. 2, pp. 167–170, 2005. View at Publisher · View at Google Scholar · View at Scopus
  23. S. E. Anderson, D. Nonaka, S. Chuai et al., “p53, epidermal growth factor, and platelet-derived growth factor in uterine leiomyosarcoma and leiomyomas,” International Journal of Gynecological Cancer, vol. 16, no. 2, pp. 849–853, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. R. G. Maki, D. R. D'Adamo, M. L. Keohan et al., “Phase II study of sorafenib in patients with metastatic or recurrent sarcomas,” Journal of Clinical Oncology, vol. 27, no. 19, pp. 3133–3140, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. M. L. Hensley, M. W. Sill, D. R. Scribner Jr. et al., “Sunitinib malate in the treatment of recurrent or persistent uterine leiomyosarcoma: a Gynecologic Oncology Group phase II study,” Gynecologic Oncology, vol. 115, no. 3, pp. 460–465, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. S. T. Mahmood, S. Agresta, C. E. Vigil et al., “Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma,” International Journal of Cancer, vol. 129, no. 8, pp. 1963–1969, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. W. T. A. Van Der Graaf, J.-Y. Blay, S. P. Chawla et al., “Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial,” The Lancet, vol. 379, no. 9829, pp. 1879–1886, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. S. Sleijfer, I. Ray-Coquard, Z. Papai et al., “Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC Study 62043),” Journal of Clinical Oncology, vol. 27, no. 19, pp. 3126–3132, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Arita, F. Kikkawa, H. Kajiyama et al., “Prognostic importance of vascular endothelial growth factor and its receptors in the uterine sarcoma,” International Journal of Gynecological Cancer, vol. 15, no. 2, pp. 329–336, 2005. View at Publisher · View at Google Scholar · View at Scopus
  30. K. Mayerhofer, P. Lozanov, K. Bodner et al., “Ki-67 and vascular endothelial growth factor expression in uterine leiomyosarcoma,” Gynecologic Oncology, vol. 92, no. 1, pp. 175–179, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Sanci, C. Dikis, S. Inan, E. Turkoz, N. Dicle, and C. Ispahi, “Immunolocalization of VEGF, VEGF receptors, EGF-R and Ki-67 in leiomyoma, cellular leiomyoma and leiomyosarcoma,” Acta Histochemica, vol. 113, no. 3, pp. 317–325, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Poncelet, R. Fauvet, G. Feldmann, F. Walker, P. Madelenat, and E. Darai, “Prognostic value of von Willebrand factor, CD34, CD31, and vascular endothelial growth factor expression in women with uterine leiomyosarcomas,” Journal of Surgical Oncology, vol. 86, no. 2, pp. 84–90, 2004. View at Publisher · View at Google Scholar · View at Scopus
  33. J. D. Wright, M. A. Powell, J. S. Rader, D. G. Mutch, and R. K. Gibb, “Bevacizumab therapy in patients with recurrent uterine neoplasms,” Anticancer Research, vol. 27, no. 5, pp. 3525–3528, 2007. View at Google Scholar · View at Scopus
  34. M. Takano, Y. Kikuchi, N. Susumu et al., “Complete remission of recurrent and refractory uterine epithelioid leimyosarcoma using weekly administration of bevacizumab and temozolomide,” European Journal of Obstetrics Gynecology & Reproductive Biology, vol. 157, no. 2, pp. 236–238, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. W. Ren, B. Korchin, G. Lahat et al., “Combined vascular endothelial growth factor receptor/epidermal growth factor receptor blockade with chemotherapy for treatment of local, uterine, and metastatic soft tissue sarcoma,” Clinical Cancer Research, vol. 14, no. 17, pp. 5466–5475, 2008. View at Publisher · View at Google Scholar · View at Scopus
  36. S. Sahebjam, P. L. Bedard, V. Castonguay et al., “A phase i study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503),” British Journal of Cancer, vol. 109, no. 4, pp. 943–949, 2013. View at Publisher · View at Google Scholar · View at Scopus
  37. H. J. MacKay, R. J. Buckanovich, H. Hirte et al., “A phase II study single agent of aflibercept (VEGF Trap) in patients with recurrent or metastatic gynecologic carcinosarcomas and uterine leiomyosarcoma. A trial of the Princess Margaret Hospital, Chicago and California Cancer Phase II Consortia,” Gynecologic Oncology, vol. 125, no. 1, pp. 136–140, 2012. View at Publisher · View at Google Scholar · View at Scopus
  38. J. S. Ross and J. A. Fletcher, “The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy,” Oncologist, vol. 3, no. 4, pp. 237–252, 1998. View at Google Scholar · View at Scopus
  39. F. Amant, V. Vloeberghs, H. Woestenborghs et al., “ERBB-2 gene overexpression and amplification in uterine sarcomas,” Gynecologic Oncology, vol. 95, no. 3, pp. 583–587, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. L. J. Layfield, K. Liu, R. Dodge, and S. H. Barsky, “Uterine smooth muscle tumors: utility of classification by proliferation, ploidy, and prognostic markers versus traditional histopathology,” Archives of Pathology and Laboratory Medicine, vol. 124, no. 2, pp. 221–227, 2000. View at Google Scholar · View at Scopus
  41. M. Zafrakas, L. Zepiridis, T. D. Theodoridis et al., “ERBB2 (HER2) protein expression in uterine sarcomas,” European Journal of Gynaecological Oncology, vol. 30, no. 3, pp. 292–294, 2009. View at Google Scholar · View at Scopus
  42. G. Sette, V. Salvati, L. Memeo et al., “EGFR inhibition abrogates leiomyosarcoma cell chemoresistance through inactivation of survival pathways and impairment of CSC potential,” PLoS ONE, vol. 7, no. 10, Article ID e46891, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. T. Gloudemans, I. Prinsen, J. A. M. Van Unnik, C. J. M. Lips, W. Den Otter, and J. S. Sussenbach, “Insulin-like growth factor gene expression in human smooth muscle tumors,” Cancer Research, vol. 50, no. 20, pp. 6689–6695, 1990. View at Google Scholar · View at Scopus
  44. T. H. Vu, C. Yballe, S. Boonyanit, and A. R. Hoffman, “Insulin-like growth factor II in uterine smooth-muscle tumors: maintenance of genomic imprinting in leiomyomata and loss of imprinting in leiomyosarcomata,” Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 5, pp. 1670–1676, 1995. View at Google Scholar · View at Scopus
  45. P. Schöffski, D. Adkins, J.-Y. Blay et al., “An open-label, phase 2 study evaluating the efficacy and safety of the anti-IGF-1R antibody cixutumumab in patients with previously treated advanced or metastatic soft-tissue sarcoma or Ewing family of tumours,” European Journal of Cancer, vol. 49, no. 15, pp. 3219–3228, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. V. M. Macaulay, M. R. Middleton, A. S. Protheroe et al., “Phase I study of humanized monoclonal antibody AVE1642 directed against the type 1 insulin-like growth factor receptor (IGF-1R), administered in combination with anticancer therapies to patients with advanced solid tumors,” Annals of Oncology, vol. 24, no. 3, pp. 784–791, 2013. View at Publisher · View at Google Scholar · View at Scopus
  47. R. Quek, Q. Wang, J. A. Morgan et al., “Combination mTOR and IGF-1R inhibition: phase I trial of everolimus and figitumumab in patients with advanced sarcomas and other solid tumors,” Clinical Cancer Research, vol. 17, no. 4, pp. 871–879, 2011. View at Publisher · View at Google Scholar · View at Scopus
  48. K. Makino, K. Kawamura, W. Sato, N. Kawamura, T. Fujimoto, and Y. Terada, “Inhibition of uterine sarcoma cell growth through suppression of endogenous tyrosine kinase B signaling,” PLoS ONE, vol. 7, no. 7, Article ID e41049, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. E. Hernando, E. Charytonowicz, M. E. Dudas et al., “The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas,” Nature Medicine, vol. 13, no. 6, pp. 748–753, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Dhingra, M. E. Rodriguez, Q. Shen et al., “Constitutive activation with overexpression of the mTORC2-phospholipase D1 pathway in uterine leiomyosarcoma and STUMP: morphoproteomic analysis with therapeutic implications,” International Journal of Clinical and Experimental Pathology, vol. 4, no. 2, pp. 134–146, 2011. View at Google Scholar · View at Scopus
  51. N. Hay and N. Sonenberg, “Upstream and downstream of mTOR,” Genes and Development, vol. 18, no. 16, pp. 1926–1945, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. N. Setsu, H. Yamamoto, K. Kohashi et al., “The Akt/mammalian target of rapamycin pathway is activated and associated with adverse prognosis in soft tissue leiomyosarcomas,” Cancer, vol. 118, no. 6, pp. 1637–1648, 2012. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Li, T. Takeda, K. Tsuiji et al., “Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells,” International Journal of Gynecological Cancer, vol. 23, no. 5, pp. 803–808, 2013. View at Publisher · View at Google Scholar · View at Scopus
  54. T. F. Wong, T. Takeda, B. Li et al., “Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition,” Gynecologic Oncology, vol. 122, no. 1, pp. 141–148, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. T. F. Wong, T. Takeda, B. Li et al., “Curcumin targets the AKT-mTOR pathway for uterine leiomyosarcoma tumor growth suppression,” International Journal of Clinical Oncology, vol. 19, no. 2, pp. 354–363, 2014. View at Publisher · View at Google Scholar · View at Scopus
  56. G. D. Demetri, S. P. Chawla, I. Ray-Coquard et al., “Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy,” Journal of Clinical Oncology, vol. 31, no. 19, pp. 2485–2492, 2013. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Okuno, H. Bailey, M. R. Mahoney et al., “A phase 2 study of temsirolimus (CCI-779) in patients with soft tissue sarcomas: a study of the Mayo phase 2 consortium (P2C),” Cancer, vol. 117, no. 15, pp. 3468–3475, 2011. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Martin-Liberal, M. Gil-Martín, M. Sáinz-Jaspeado et al., “Phase I study and preclinical efficacy evaluation of the mTOR inhibitor sirolimus plus gemcitabine in patients with advanced solid tumours,” British Journal of Cancer, vol. 111, no. 5, pp. 858–865, 2014. View at Publisher · View at Google Scholar · View at Scopus
  59. O. Merimsky, Y. Gorzalczany, and R. Sagi-Eisenberg, “Molecular impacts of rapamycin-based drug combinations: combining rapamycin with gemcitabine or imatinib mesylate (Gleevec) in a human leiomyosarcoma model,” International Journal of Oncology, vol. 31, no. 1, pp. 225–232, 2007. View at Google Scholar · View at Scopus
  60. O. Merimsky, “Targeting metastatic leiomyosarcoma by rapamycin plus gemcitabine: an intriguing clinical observation,” International Journal of Molecular Medicine, vol. 14, no. 5, pp. 931–935, 2004. View at Google Scholar · View at Scopus
  61. K. J. Brewer Savannah, E. G. Demicco, K. Lusby et al., “Dual targeting of mTOR and Aurora-A kinase for the treatment of uterine leiomyosarcoma,” Clinical Cancer Research, vol. 18, no. 17, pp. 4633–4645, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. K. Saito-Diaz, T. W. Chen, X. Wang et al., “The way Wnt works: components and mechanism,” Growth Factors, vol. 31, no. 1, pp. 1–31, 2013. View at Publisher · View at Google Scholar · View at Scopus
  63. M. A. de Graaff, A.-M. Cleton-Jansen, K. Szuhai, and J. V. M. G. Bovée, “Mediator complex subunit 12 exon 2 mutation analysis in different subtypes of smooth muscle tumors confirms genetic heterogeneity,” Human Pathology, vol. 44, no. 8, pp. 1597–1604, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. W. Kildal, M. Pradhan, V. M. Abeler, G. B. Kristensen, and H. E. Danielsen, “Beta-catenin expression in uterine sarcomas and its relation to clinicopathological parameters,” European Journal of Cancer, vol. 45, no. 13, pp. 2412–2417, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Voronkov and S. Krauss, “Wnt/beta-catenin signaling and small molecule inhibitors,” Current Pharmaceutical Design, vol. 19, no. 4, pp. 634–664, 2013. View at Publisher · View at Google Scholar · View at Scopus
  66. B. Edris, I. Espinosa, T. Mühlenberg et al., “ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour,” The Journal of Pathology, vol. 227, no. 2, pp. 223–233, 2012. View at Publisher · View at Google Scholar · View at Scopus
  67. H. Mitsui, K. Shibata, Y. Mano et al., “The expression and characterization of endoglin in uterine leiomyosarcoma,” Clinical and Experimental Metastasis, vol. 30, no. 6, pp. 731–740, 2013. View at Publisher · View at Google Scholar · View at Scopus
  68. W. Shan, P. Y. Akinfenwa, K. B. Savannah et al., “A small-molecule inhibitor targeting the mitotic spindle checkpoint impairs the growth of uterine leiomyosarcoma,” Clinical Cancer Research, vol. 18, no. 12, pp. 3352–3365, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Li, T. Liu, C. Ivan et al., “Enhanced cytotoxic effects of combined valproic acid and the aurora kinase inhibitor VE465 on gynecologic cancer cells,” Frontiers in Oncology, vol. 3, article 58, 2013. View at Publisher · View at Google Scholar · View at Scopus
  70. Hyman and National Cancer Institute (NCI), “Alisertib in treating patients with recurrent or persistent leiomyosarcoma of the uterus,” Tech. Rep. NCT01637961, 2014. View at Google Scholar
  71. A. J. Levine and M. Oren, “The first 30 years of p53: growing ever more complex,” Nature Reviews Cancer, vol. 9, no. 10, pp. 749–758, 2009. View at Publisher · View at Google Scholar · View at Scopus
  72. P. Ragazzini, G. Gamberi, L. Pazzaglia et al., “Amplification of CDK4, MDM2, SAS and GLI genes in leiomyosarcoma, alveolar and embryonal rhabdomyosarcoma,” Histology and Histopathology, vol. 19, no. 3, p. 1013, 2004. View at Google Scholar · View at Scopus
  73. U. N. M. Rao, S. D. Finkelstein, and M. W. Jones, “Comparative immunohistochemical and molecular analysis of uterine and extrauterine leiomyosarcomas,” Modern Pathology, vol. 12, no. 11, pp. 1001–1009, 1999. View at Google Scholar · View at Scopus
  74. R. Blom, C. Guerrieri, O. Stål, H. Malmström, and E. Simonsen, “Leiomyosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases,” Gynecologic Oncology, vol. 68, no. 1, pp. 54–61, 1998. View at Publisher · View at Google Scholar · View at Scopus
  75. K. L. Hall, M. G. Teneriello, R. R. Taylor et al., “Analysis of Ki-ras, p53, and MDM2 genes in uterine leiomyomas and leiomyosarcomas,” Gynecologic Oncology, vol. 65, no. 2, pp. 330–335, 1997. View at Publisher · View at Google Scholar · View at Scopus
  76. J.-C. Carry and C. Garcia-Echeverria, “Inhibitors of the p53/hdm2 protein-protein interaction-path to the clinic,” Bioorganic and Medicinal Chemistry Letters, vol. 23, no. 9, pp. 2480–2485, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. Q. Ding, Z. Zhang, J.-J. Liu et al., “Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development,” Journal of Medicinal Chemistry, vol. 56, no. 14, pp. 5979–5983, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. D. Sun, Z. Li, Y. Rew et al., “Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development,” Journal of Medicinal Chemistry, vol. 57, no. 4, pp. 1454–1472, 2014. View at Publisher · View at Google Scholar · View at Scopus
  79. A. Y. Saiki, S. Caenepeel, D. Yu et al., “MDM2 antagonists synergize broadly and robustly with compounds targeting fundamental oncogenic signaling pathways,” Oncotarget, vol. 5, no. 8, pp. 2030–2043, 2014. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Grunstein, “Histone acetylation in chromatin structure and transcription,” Nature, vol. 389, no. 6649, pp. 349–352, 1997. View at Publisher · View at Google Scholar
  81. L. de Leval, D. Waltregny, J. Boniver, R. H. Young, V. Castronovo, and E. Oliva, “Use of histone deacetylase 8 (HDAC8), a new marker of smooth muscle differentiation, in the classification of mesenchymal tumors of the uterus,” American Journal of Surgical Pathology, vol. 30, no. 3, pp. 319–327, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Hrzenjak, F. Moinfar, M.-L. Kremser et al., “Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo,” Molecular Cancer, vol. 9, article 49, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. P. Quan, F. Moinfar, I. Kufferath et al., “Effects of targeting endometrial stromal sarcoma cells via histone deacetylase and PI3K/AKT/mTOR signaling,” Anticancer Research, vol. 34, no. 6, pp. 2883–2897, 2014. View at Google Scholar · View at Scopus
  84. A. Atmaca, S.-E. Al-Batran, A. Maurer et al., “Valproic acid (VPA) in patients with refractory advanced cancer: a dose escalating phase I clinical trial,” British Journal of Cancer, vol. 97, no. 2, pp. 177–182, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. P. Münster, D. Marchion, E. Bicaku et al., “Phase I trial of histone deacetylase inhibition by valproic acid followed by the topoisomerase II inhibitor epirubicin in advanced solid tumors: a clinical and translational study,” Journal of Clinical Oncology, vol. 25, no. 15, pp. 1979–1985, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. B. Edris, K. Weiskopf, A. K. Volkmer et al., “Antibody therapy targeting the CD47 protein is effective in a model of aggressive metastatic leiomyosarcoma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 17, pp. 6656–6661, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. N. Ü. Çomunoğlu, H. Durak, C. Çomunoğlu et al., “Expression of cyclooxygenase-2, c-kit, progesterone and estrogen receptors in uterine smooth muscle tumors: differential diagnosis,” APMIS, vol. 115, no. 6, pp. 726–735, 2007. View at Publisher · View at Google Scholar · View at Scopus
  88. C.-H. Lee, D. A. Turbin, Y.-C. V. Sung et al., “A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors,” Modern Pathology, vol. 22, no. 12, pp. 1519–1531, 2009. View at Publisher · View at Google Scholar · View at Scopus
  89. M. M. Leitao, R. A. Soslow, D. Nonaka et al., “Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma,” Cancer, vol. 101, no. 6, pp. 1455–1462, 2004. View at Publisher · View at Google Scholar · View at Scopus
  90. Y. Rodríguez, D. Báez, F. M. de Oca et al., “Comparative analysis of the ERalpha/ERbeta ratio and neurotensin and its high-affinity receptor in myometrium, uterine leiomyoma, atypical leiomyoma, and leiomyosarcoma,” International Journal of Gynecological Pathology, vol. 30, no. 4, pp. 354–363, 2011. View at Publisher · View at Google Scholar · View at Scopus
  91. E. Thanopoulou, K. Thway, K. Khabra, and I. Judson, “Treatment of hormone positive uterine leiomyosarcoma with aromatase inhibitors,” Clinical Sarcoma Research, vol. 4, article 5, 2014. View at Publisher · View at Google Scholar
  92. J. Hu, V. Khanna, M. Jones, and U. Surti, “Genomic alterations in uterine leiomyosarcomas: potential markers for clinical diagnosis and prognosis,” Genes Chromosomes and Cancer, vol. 31, no. 2, pp. 117–124, 2001. View at Publisher · View at Google Scholar · View at Scopus
  93. Y.-L. Zhai, T. Nikaido, A. Orii, A. Horiuchi, T. Toki, and S. Fujii, “Frequent occurrence of loss of heterozygosity among tumor suppressor genes in uterine leiomyosarcoma,” Gynecologic Oncology, vol. 75, no. 3, pp. 453–459, 1999. View at Publisher · View at Google Scholar · View at Scopus
  94. K. Kawaguchi, Y. Oda, T. Saito et al., “Mechanisms of inactivation of the p16INK4a gene in leiomyosarcoma of soft tissue: decreased p16 expression correlates with promoter methylation and poor prognosis,” The Journal of Pathology, vol. 201, no. 3, pp. 487–495, 2003. View at Publisher · View at Google Scholar
  95. J. H. Francis, R. A. Kleinerman, J. M. Seddon, and D. H. Abramson, “Increased risk of secondary uterine leiomyosarcoma in hereditary retinoblastoma,” Gynecologic Oncology, vol. 124, no. 2, pp. 254–259, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. M. C. Hollander, G. M. Blumenthal, and P. A. Dennis, “PTEN loss in the continuum of common cancers, rare syndromes and mouse models,” Nature Reviews Cancer, vol. 11, no. 4, pp. 289–301, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. V. Stambolic, A. Suzuki, J. L. de la Pompa et al., “Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN,” Cell, vol. 95, no. 1, pp. 29–39, 1998. View at Publisher · View at Google Scholar · View at Scopus
  98. M. S. Neshat, I. K. Mellinghoff, C. Tran et al., “Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 18, pp. 10314–10319, 2001. View at Publisher · View at Google Scholar · View at Scopus
  99. M. Patel, N. C. Gomez, A. W. McFadden et al., “PTEN deficiency mediates a reciprocal response to IGFI and mTOR inhibition,” Molecular Cancer Research, vol. 12, no. 11, pp. 1610–1620, 2014. View at Publisher · View at Google Scholar · View at Scopus
  100. L. S. Steelman, P. M. Navolanic, M. L. Sokolosky et al., “Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors,” Oncogene, vol. 27, no. 29, pp. 4086–4095, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. S. Nag, J. Qin, K. S. Srivenugopal, M. Wang, and R. Zhang, “The MDM2-p53 pathway revisited,” Journal of Biomedical Research, vol. 27, no. 4, pp. 254–271, 2013. View at Publisher · View at Google Scholar · View at Scopus
  102. D. Xing, G. Scangas, M. Nitta et al., “A role for BRCA1 in uterine leiomyosarcoma,” Cancer Research, vol. 69, no. 21, pp. 8231–8235, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. S. M. B. Nijman and S. H. Friend, “Cancer: potential of the synthetic lethality principle,” Science, vol. 342, no. 6160, pp. 809–811, 2013. View at Publisher · View at Google Scholar · View at Scopus
  104. P. C. Fong, D. S. Boss, T. A. Yap et al., “Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers,” The New England Journal of Medicine, vol. 361, no. 2, pp. 123–134, 2009. View at Publisher · View at Google Scholar · View at Scopus
  105. K. J. Dedes, D. Wetterskog, A. M. Mendes-Pereira et al., “PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors,” Science Translational Medicine, vol. 2, no. 53, Article ID 53ra75, 2010. View at Publisher · View at Google Scholar · View at Scopus
  106. I. Chew and E. Oliva, “Endometrial stromal sarcomas: a review of potential prognostic factors,” Advances in Anatomic Pathology, vol. 17, no. 2, pp. 113–121, 2010. View at Publisher · View at Google Scholar · View at Scopus
  107. E. Oliva, M. L. Carcangiu, S. G. Carinelli et al., “Tumours of the uterine corpus—mesenchymal tumours,” in WHO Classification of Tumours of Female Reproductive Organs, R. J. Kurman, Ed., pp. 135–147, 4th edition, 2014. View at Google Scholar
  108. F. Amant, A. De Knijf, B. Van Calster et al., “Clinical study investigating the role of lymphadenectomy, surgical castration and adjuvant hormonal treatment in endometrial stromal sarcoma,” British Journal of Cancer, vol. 97, no. 9, pp. 1194–1199, 2007. View at Publisher · View at Google Scholar · View at Scopus
  109. T. L. Beck, P. K. Singhal, H. M. Ehrenberg et al., “Endometrial stromal sarcoma: analysis of recurrence following adjuvant treatment,” Gynecologic Oncology, vol. 125, no. 1, pp. 141–144, 2012. View at Publisher · View at Google Scholar · View at Scopus
  110. X. Cheng, G. Yang, K. M. Schmeler et al., “Recurrence patterns and prognosis of endometrial stromal sarcoma and the potential of tyrosine kinase-inhibiting therapy,” Gynecologic Oncology, vol. 121, no. 2, pp. 323–327, 2011. View at Publisher · View at Google Scholar · View at Scopus
  111. P. Cossu-Rocca, M. Contini, M. G. Uras et al., “Tyrosine kinase receptor status in endometrial stromal sarcoma: an immunohistochemical and genetic-molecular analysis,” International Journal of Gynecological Pathology, vol. 31, no. 6, pp. 570–579, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. B. Liegl, O. Reich, F. F. Nogales, and S. Regauer, “PDGF-α and PDGF-β are expressed in endometrial stromal sarcoma: a potential therapeutic target for tyrosine kinase inhibitors?” Histopathology, vol. 49, no. 5, pp. 545–546, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. J.-Y. Park, K.-R. Kim, and J.-H. Nam, “Immunohistochemical analysis for therapeutic targets and prognostic markers in low-grade endometrial stromal sarcoma,” International Journal of Gynecological Cancer, vol. 23, no. 1, pp. 81–89, 2013. View at Publisher · View at Google Scholar · View at Scopus
  114. R. Sardinha, T. Hernández, S. Fraile et al., “Endometrial stromal tumors: immunohistochemical and molecular analysis of potential targets of tyrosine kinase inhibitors,” Clinical Sarcoma Research, vol. 3, article 3, 2013. View at Publisher · View at Google Scholar
  115. S.-I. Iwasaki, T. Sudo, M. Miwa et al., “Endometrial stromal sarcoma: clinicopathological and immunophenotypic study of 16 cases,” Archives of Gynecology and Obstetrics, vol. 288, no. 2, pp. 385–391, 2013. View at Publisher · View at Google Scholar · View at Scopus
  116. M. E. Kalender, A. Sevinc, M. Yilmaz, C. Ozsarac, and C. Camci, “Detection of complete response to imatinib mesylate (Glivec/Gleevec) with 18F-FDG PET/CT for low-grade endometrial stromal sarcoma,” Cancer Chemotherapy and Pharmacology, vol. 63, no. 3, pp. 555–559, 2009. View at Google Scholar
  117. A. Trojan, M. Montemurro, M. Kamel, and G. Kristiansen, “Successful PDGFR-α/β targeting with imatinib in uterine sarcoma,” Annals of Oncology, vol. 20, no. 11, pp. 1898–1899, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. C. Lan, X. Huang, S. Lin, M. Cai, and J. Liu, “Endometrial stromal sarcoma arising from endometriosis: a clinicopathological study and literature review,” Gynecologic and Obstetric Investigation, vol. 74, no. 4, pp. 288–297, 2012. View at Publisher · View at Google Scholar · View at Scopus
  119. F. Moinfar, M. Gogg-Kamerer, A. Sommersacher et al., “Endometrial stromal sarcomas frequently express epidermal growth factor receptor (EGFR, HER-1): potential basis for a new therapeutic approach,” The American Journal of Surgical Pathology, vol. 29, no. 4, pp. 485–489, 2005. View at Publisher · View at Google Scholar · View at Scopus
  120. G. Capobianco, F. Pili, M. Contini et al., “Analysis of epidermal growth factor receptor (EGFR) status in endometrial stromal sarcoma,” European Journal of Gynaecological Oncology, vol. 33, no. 6, pp. 629–632, 2012. View at Google Scholar · View at Scopus
  121. P. A. Cassier, A. Lefranc, E. Y Amela et al., “A phase II trial of panobinostat in patients with advanced pretreated soft tissue sarcoma. A study from the French Sarcoma Group,” British Journal of Cancer, vol. 109, no. 4, pp. 909–914, 2013. View at Publisher · View at Google Scholar · View at Scopus
  122. A. Hrzenjak, F. Moinfar, M.-L. Kremser et al., “Valproate inhibition of histone deacetylase 2 affects differentiation and decreases proliferation of endometrial stromal sarcoma cells,” Molecular Cancer Therapeutics, vol. 5, no. 9, pp. 2203–2210, 2006. View at Publisher · View at Google Scholar · View at Scopus
  123. A. Hrzenjak, M.-L. Kremser, B. Strohmeier, F. Moinfar, K. Zatloukal, and H. Denk, “SAHA induces caspase-independent, autophagic cell death of endometrial stromal sarcoma cells by influencing the mTOR pathway,” Journal of Pathology, vol. 216, no. 4, pp. 495–504, 2008. View at Publisher · View at Google Scholar · View at Scopus
  124. T.-I. Wu, H.-H. Chou, C.-J. Yeh et al., “Clinicopathologic parameters and immunohistochemical study of endometrial stromal sarcomas,” International Journal of Gynecological Pathology, vol. 32, no. 5, pp. 482–492, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. C.-K. Jung, J.-H. Jung, A. Lee et al., “Diagnostic use of nuclear β-catenin expression for the assessment of endometrial stromal tumors,” Modern Pathology, vol. 21, no. 6, pp. 756–763, 2008. View at Publisher · View at Google Scholar · View at Scopus
  126. S. Kurihara, Y. Oda, Y. Ohishi et al., “Coincident expression of β-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas,” Modern Pathology, vol. 23, no. 2, pp. 225–234, 2010. View at Publisher · View at Google Scholar · View at Scopus
  127. T. L. Ng, A. M. Gown, T. S. Barry et al., “Nuclear beta-catenin in mesenchymal tumors,” Modern Pathology, vol. 18, no. 1, pp. 68–74, 2005. View at Publisher · View at Google Scholar · View at Scopus
  128. C.-H. Lee, R. H. Ali, M. Rouzbahman et al., “Cyclin D1 as a diagnostic immunomarker for endometrial stromal sarcoma with YWHAE-FAM22 rearrangement,” American Journal of Surgical Pathology, vol. 36, no. 10, pp. 1562–1570, 2012. View at Publisher · View at Google Scholar · View at Scopus
  129. Y. J. Ioffe, A. J. Li, C. S. Walsh et al., “Hormone receptor expression in uterine sarcomas: prognostic and therapeutic roles,” Gynecologic Oncology, vol. 115, no. 3, pp. 466–471, 2009. View at Publisher · View at Google Scholar · View at Scopus
  130. S. Kurihara, Y. Oda, Y. Ohishi et al., “Endometrial stromal sarcomas and related high-grade sarcomas: immunohistochemical and molecular genetic study of 31 cases,” American Journal of Surgical Pathology, vol. 32, no. 8, pp. 1228–1238, 2008. View at Publisher · View at Google Scholar · View at Scopus
  131. O. Reich, S. Regauer, W. Urdl, M. Lahousen, and R. Winter, “Expression of oestrogen and progesterone receptors in low-grade endometrial stromal sarcomas,” British Journal of Cancer, vol. 82, no. 5, pp. 1030–1034, 2000. View at Publisher · View at Google Scholar · View at Scopus
  132. A. Yoon, J.-Y. Park, J.-Y. Park et al., “Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: a multicenter review of 114 cases,” Gynecologic Oncology, vol. 132, no. 1, pp. 70–75, 2014. View at Publisher · View at Google Scholar · View at Scopus
  133. M. C. Chu, G. Mor, C. Lim, W. Zheng, V. Parkash, and P. E. Schwartz, “Low-grade endometrial stromal sarcoma: hormonal aspects,” Gynecologic Oncology, vol. 90, no. 1, pp. 170–176, 2003. View at Publisher · View at Google Scholar · View at Scopus
  134. M. C. Lim, S. Lee, and S.-S. Seo, “Megestrol acetate therapy for advanced low-grade endometrial stromal sarcoma,” Onkologie, vol. 33, no. 5, pp. 260–262, 2010. View at Publisher · View at Google Scholar · View at Scopus
  135. M. Mizuno, Y. Yatabe, A. Nawa, and T. Nakanishi, “Long-term medroxyprogesterone acetate therapy for low-grade endometrial stromal sarcoma,” International Journal of Clinical Oncology, vol. 17, no. 4, pp. 348–354, 2012. View at Publisher · View at Google Scholar · View at Scopus
  136. K. Nakayama, M. Ishikawa, Y. Nagai, N. Yaegashi, Y. Aoki, and K. Miyazaki, “Prolonged long-term survival of low-grade endometrial stromal sarcoma patients with lung metastasis following treatment with medroxyprogesterone acetate,” International Journal of Clinical Oncology, vol. 15, no. 2, pp. 179–183, 2010. View at Publisher · View at Google Scholar · View at Scopus
  137. D. Pink, T. Lindner, A. Mrozek et al., “Harm or benefit of hormonal treatment in metastatic low-grade endometrial stromal sarcoma: single center experience with 10 cases and review of the literature,” Gynecologic Oncology, vol. 101, no. 3, pp. 464–469, 2006. View at Publisher · View at Google Scholar · View at Scopus
  138. L. M. Ramondetta, A. J. Johnson, C. C. Sun et al., “Phase 2 trial of mifepristone (RU-486) in advanced or recurrent endometrioid adenocarcinoma or low-grade endometrial stromal sarcoma,” Cancer, vol. 115, no. 9, pp. 1867–1874, 2009. View at Publisher · View at Google Scholar · View at Scopus
  139. G. Garg, J. P. Shah, E. P. Toy, C. S. Bryant, S. Kumar, and R. T. Morris, “Stage IA vs. IB endometrial stromal sarcoma: does the new staging system predict survival?” Gynecologic Oncology, vol. 118, no. 1, pp. 8–13, 2010. View at Publisher · View at Google Scholar · View at Scopus
  140. E. J. Tanner, K. Garg, M. M. Leitao Jr., R. A. Soslow, and M. L. Hensley, “High grade undifferentiated uterine sarcoma: surgery, treatment, and survival outcomes,” Gynecologic Oncology, vol. 127, no. 1, pp. 27–31, 2012. View at Publisher · View at Google Scholar · View at Scopus
  141. F. Amant, T. Tousseyn, L. Coenegrachts, J. Decloedt, P. Moerman, and M. Debiec-Rychter, “Case report of a poorly differentiated uterine tumour with t(10;17) translocation and neuroectodermal phenotype,” Anticancer Research, vol. 31, no. 6, pp. 2367–2371, 2011. View at Google Scholar · View at Scopus
  142. K. Leunen, F. Amant, M. Debiec-Rychter et al., “Endometrial stromal sarcoma presenting as postpartum haemorrhage: report of a case with a sole t(10;17)(q22;p13) translocation,” Gynecologic Oncology, vol. 91, no. 1, pp. 265–271, 2003. View at Publisher · View at Google Scholar
  143. F. Micci, C. U. Walter, M. R. Teixeira et al., “Cytogenetic and molecular genetic analyses of endometrial stromal sarcoma: nonrandom involvement of chromosome arms 6p and 7p and confirmation of JAZF1/JJAZ1 gene fusion in t(7;17),” Cancer Genetics and Cytogenetics, vol. 144, no. 2, pp. 119–124, 2003. View at Publisher · View at Google Scholar · View at Scopus
  144. S. Regauer, W. Emberger, O. Reich, and R. Pfragner, “Cytogenetic analyses of two new cases of endometrial stromal sarcoma—non-random reciprocal translocation t(10;17)(q22;p13) correlates with fibrous ESS,” Histopathology, vol. 52, no. 6, pp. 780–783, 2008. View at Publisher · View at Google Scholar · View at Scopus
  145. C. H. Lee, W. B. Ou, A. Mariño-Enriquez et al., “14-3-3 fusion oncogenes in high-grade endometrial stromal sarcoma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 3, pp. 929–934, 2012. View at Publisher · View at Google Scholar
  146. S. Croce, I. Hostein, A. Ribeiro et al., “YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: genetic and pathological correlations,” Modern Pathology, vol. 26, no. 10, pp. 1390–1400, 2013. View at Publisher · View at Google Scholar · View at Scopus
  147. T. Mitsuhashi, M. Nakayama, S. Sakurai et al., “KIT-negative undifferentiated endometrial sarcoma with the amplified epidermal growth factor receptor gene showing a temporary response to imatinib mesylate,” Annals of Diagnostic Pathology, vol. 11, no. 1, pp. 49–54, 2007. View at Publisher · View at Google Scholar · View at Scopus
  148. A. Salvatierra, A. Tarrats, C. Gomez, J. M. Sastre, and C. Balaña, “A case of c-kit positive high-grade stromal endometrial sarcoma responding to Imatinib Mesylate,” Gynecologic Oncology, vol. 101, no. 3, pp. 545–547, 2006. View at Publisher · View at Google Scholar · View at Scopus
  149. C.-H. Lee, L. N. Hoang, S. Yip et al., “Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement,” Modern Pathology, vol. 27, no. 5, pp. 751–757, 2014. View at Publisher · View at Google Scholar · View at Scopus
  150. 2012, http://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm330213.htm.
  151. A. Hrzenjak, M. Tippl, M.-L. Kremser et al., “Inverse correlation of secreted frizzled-related protein 4 and β-catenin expression in endometrial stromal sarcomas,” Journal of Pathology, vol. 204, no. 1, pp. 19–27, 2004. View at Publisher · View at Google Scholar · View at Scopus
  152. K. E. O'Reilly, F. Rojo, Q.-B. She et al., “mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt,” Cancer Research, vol. 66, no. 3, pp. 1500–1508, 2006. View at Publisher · View at Google Scholar · View at Scopus
  153. C. Qian, C.-J. Lai, R. Bao et al., “Cancer network disruption by a single molecule inhibitor targeting both histone deacetylase activity and phosphatidylinositol 3-kinase signaling,” Clinical Cancer Research, vol. 18, no. 15, pp. 4104–4113, 2012. View at Publisher · View at Google Scholar · View at Scopus
  154. C.-J. Lai, R. Bao, X. Tao et al., “CUDC-101, a multitargeted inhibitor of histone deacetylase, epidermal growth factor receptor, and human epidermal growth factor receptor 2, exerts potent anticancer activity,” Cancer Research, vol. 70, no. 9, pp. 3647–3656, 2010. View at Publisher · View at Google Scholar · View at Scopus