Updates in therapy for uterine serous carcinoma

Current Opinion in Obstetrics and Gynecology

Volumn 25, Issue 1, 2013, Pages 29-37

  Roque, Dana M ^a   Santin, Alessandro D ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

epothilone; HER2 Neu; mTOR inhibitor; PI3KCA; uterine serous carcinoma

Indexed keywords

BETA TUBULIN; BEVACIZUMAB; BRCA1 PROTEIN; CARBOPLATIN; CISPLATIN; CLAUDIN 3; CLAUDIN 4; CYCLIN E; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPOTHILONE B; EPOTHILONE DERIVATIVE; F BOX PROTEIN; FIBRONECTIN; IXABEPILONE; MAMMALIAN TARGET OF RAPAMYCIN; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN P53; SOMATOMEDIN C RECEPTOR; UVOMORULIN; VASCULOTROPIN; VIMENTIN;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; BRACHYTHERAPY; CANCER CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER RADIOTHERAPY; COMPLEMENT DEPENDENT CYTOTOXICITY; DISEASE FREE SURVIVAL; ENDOMETRIUM CANCER; ENZYME PHOSPHORYLATION; EPITHELIAL MESENCHYMAL TRANSITION; EXOME; GENETIC ASSOCIATION; HUMAN; HYSTERECTOMY; LYMPH NODE DISSECTION; MOLECULAR MECHANICS; MOLECULAR PATHOLOGY; MONOTHERAPY; MULTIPLE CYCLE TREATMENT; OMENTECTOMY; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RADIATION DOSE FRACTIONATION; RECURRENCE FREE SURVIVAL; REVIEW; SALPINGOOOPHORECTOMY; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; UPREGULATION; UTERINE SEROUS CARCINOMA; UTERUS CARCINOMA;

CYSTADENOCARCINOMA, SEROUS; CYTOTOXINS; ENDOMETRIAL NEOPLASMS; FEMALE; HUMANS; IMMUNOTHERAPY;

EID: 84873090658     PISSN: 1040872X     EISSN: 1473656X     Source Type: Journal    
DOI: 10.1097/GCO.0b013e32835af98d     Document Type: Review

References (131)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin 2012; 62:10-29.
2. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 1983; 15:10-17.
3. Amant F, Moerman P, Neven P, et al. Endometrial cancer. Lancet 2005; 366:491-505.
4. Felix AS, Weissfeld JL, Stone RA, et al. Factors associated with Type I and Type II endometrial cancer. Cancer Causes Control 2010; 21:1851-1856.
5. Creasman WT, Odicino F, Maisonneuve P, et al. Carcinoma of the corpus uteri. FIGO 26th Annual Report on the results of treatment in Gynecological Cancer. Int J Gynaecol Obstet 2006; 95 (Suppl 1):S105-S143.
6. Lax SF, Pizer ES, Ronnett BM, et al. Comparison of estrogen and progesterone receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid carcinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation. Hum Path 1998; 29:924-931.
7. Voss MA, Ganesan R, Ludeman L, et al. Should grade 3 endometrioid endometrial carcinoma be considered a type 2 cancer: a clinical and pathological evaluation. Gynecol Oncol 2012; 124:15-20.
8. Goff BA, Kato D, Schmidt RA, et al. Uterine papillary serous carcinoma: pattern of metastatic spread. Gynecol Oncol 1994; 54:264-268.
9. Mutch DG. The more things change, the more they stay the same. Gynecol Oncol 2012; 124:3-4.
10. Wilson TO, Podratz KC, Gaffey TA, et al. Evaluation of unfavorable histologic subtypes in endometrial adenocarcinoma. Am J Obstet Gynecol 1990; 162:418-426.
11. Emons G, Fleckenstein G, Hinney B, et al. Hormonal interactions in endometrial cancer. Endocr Relat Cancer 2000; 7:227-242.
12. Hameed K, Morgan DA. Papillary adenocarcinoma of endometrium with psammoma bodies: histology and fine structure. Cancer 1972; 29:1326-1335.
13. Hamilton CA, Cheung MK, Osann K, et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br J Cancer 2006; 94:642-646.
14. Dizon DS. Treatment options for advanced endometrial carcinoma. Gynecol Oncol 2010; 117:373-381.
15. Schwartz PE. The management of serous papillary uterine cancer. Curr Opin Oncol 2006; 18:494-499.
16. Thomas M, Mariani A, Wright JD. Surgical management and adjuvant therapy for patients with uterine clear cell carcinoma: a multi-institutional review. Gynecol Oncol 2008; 108:293-297.
17. Goff BA. Uterine papillary serous carcinoma: what have we learned over the past quarter century? Gynecol Oncol 2005; 98:341-343.
18. Yoon J, Yoo S, Kim WY, et al. Para-aortic lymphadenectomy in the management of preoperative grade 1 endometrial cancer confined to the uterine corpus. Annals Surg Onc 2010; 17:3234-3240.
19. Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol 2012; 30:695-700.
20. National Comprehensive Cancer Network Practice Guidelines. Uterine Neoplasms, v 3.2012. http://www.nccn.org/professionals/physician-gls/pdf/ uterine.pdf. [Accessed 15 September 2012]
21. Sovak MA, Dupont J, Hensley ML, et al. Paclitaxel and carboplatin in the adjuvant treatment of patients with high-risk stage III and IV endometrial cancer: a retrospective study. Gynecol Oncol 2006; 103:451-457.
22. Vaidya AP, Littell R, Krasner C, et al. Treatment of uterine papillary serous carcinoma with platinum-based chemotherapy and paclitaxel. Int J Gynecol Cancer 2006; 16 (suppl 1):267-272.
23. Miller D., Filiaci V., Fleming G., et al., Randomized phase, III, noninferiority trial of first-line chemotherapy for metastatic or recurrent endometrial carcinoma: a Gynecologic Oncology Group study [late-breaking abstract]. Annual Meeting of the Society of Gynecologic Oncologists 2012, Mar 24-7, 2012, Austin, TX.
24. Gallion HH, Brunetto VL, Cibull M, et al. Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2003; 21:3808-3813.
25. Fleming GF, Brunetto VL, Cella D, et al. Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2004; 22:2159-2166.
26. Fleming GF, Filiaci VL, Bentley RC, et al. Phase III randomized trial of doxorubicin and cisplatin versus doxorubicin and 24-h paclitaxel with filgastrim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 2004; 15:1173-1178.
27. Thigpen JT, Brady MF, Homesley HD, et al. Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 2004; 22:3902-3908.
28. Homesley HD, Filiaci V, Gibbons SK, et al. A randomized phase III trial in advanced endometrial carcinoma of surgery and volume-directed radiation followed by cisplatin and doxorubicin with or without paclitaxel: a Gynecologic Oncology Group study. Gynecol Oncol 2009; 112:543-552.
29. Viswanathan AN, Macklin EA, Berkowitz R, et al. The importance of chemotherapy and radiation in uterine papillary serous carcinoma. Gynecol Oncol 2011; 123:542-547.
30. Sutton G, Axelrod JH, Bundy BN, et al. Adjuvant whole-abdominal irradiation in clinical stage I and II papillary serous or clear cell carcinoma of the endometrium: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol 2006; 100:349-354.
31. Fader AN, Drake RD, O'Malley DM, et al. Platinum/taxane-based chemotherapy with or without radiotherapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma. Cancer 2009; 115:2119-2127.
32. Fader AN, Nagel C, Axtell AE, et al. Stage II uterine papillary serous carcinoma: carboplatin/paclitaxel chemotherapy improves recurrence and survival outcomes. Gyneol Oncol 2009; 112:558-562.
33. Kelly MG, O'Malley DM, Hui P, et al. Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy. Gynecol Oncol 2005; 98:353-359.
34. Mahdavi A, Tajalli TR, Dalmar A, et al. Role of adjuvant chemotherapy in patients with early stage uterine papillary serous cancer. Int J Gynecol Cancer 2011; 21:1436-1440.
35. Kiess AP, Damast S, Makker V, et al. Five-year outcomes of adjuvant carboplatin/paclitaxel chemotherapy and intravaginal radiation for stage I-II papillary serous endometrial cancer. Gynecol Oncol 2012; 127:321-325.
36. De Leon M, Lu L, Hui P, et al. Prognostic factors and treatment-related outcomes in patients with uterine serous cancer [abstract]. J Clin Oncol 2012; 30:2012.
37. Kelly MG, O'Malley D, Hui P, et al. Patients with uterine papillary serous cancers may benefit from adjuvant platinum-based chemoradiation. Gynecol Oncol 2004; 95:469-473.
38. Alektiar KM, Makker V, Abu-Rustum NR, et al. Concurrent carboplatin/paclitaxel and intravaginal radiation in surgical stage I-II serous endometrial cancer. Gynecol Oncol 2009; 112:142-145.
39. Einstein MH, Frimer M, Kuo DY, et al. Phase II trial of adjuvant pelvic radiation 'sandwiched' between combination paclitaxel and carboplatin in women with uterine papillary serous carcinoma. Gynecol Oncol 2012; 124:21-25.
40. Giuntoli RL 2nd, Gerardi MA, Yemelyanova AV, et al. Stage I noninvasive and minimally invasive uterins serous carcinoma: comprehensive staging associated with improved survival. Int J Gynecol Cancer 2012; 22:273-279.
41. Boruta DM 2nd, Gehrig PA, Fader AN, et al. Management of women with uterine papillary serous cancer: a Society of Gynecologic Oncology (SGO) review. Gynecol Oncol 2009; 115:142-153.
42. NIH Clinical Trials. Pelvic radiation therapy or vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or stage II endometrial cancer. http://clinicaltrials.gov/ show/NCT00807768. [Accessed 15 September 2012]
43. Sherman ME. Theories of endometrial carcinogenesis. Mod Pathol 2000; 13:295-298.
44. Hecht JL, Mutter GL. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol 2006; 24:4783-4791.
45. Rosenberg P, Wingren S, Simonsen E, et al. Flow cytometric measurements of DNA index and S-phase on paraffin-embedded early stage endometrial cancer: an important prognostic indicator. Gynecol Oncol 1989; 35: 50-54.
46. Pradhan M, Abeler VM, Danielsen HE, et al. Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas. Mod Pathol 2006; 19:1227-1235.
47. Santin AD, Bellone S, Van Stedum S, et al. Amplification of c-erbB2 oncogene: a major prognostic indicator in uterine serous papillary carcinoma. Cancer 2005; 104:1391-1397.
48. Slomovitz BM, Broaddus RR, Burke TW. HER2/neu overexpression and amplification in uterine papillary serous carcinoma. J Clin Oncol 2004; 22:3126-3132.
49. Grushko TA, Filiaci VL, Mundt AJ, et al. An exploratory analysis of HER-2 amplification and overexpression in advanced endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 2008; 108:3-9.
50. Díaz-Montes TP, Ji H, Smith Sehdev AE, et al. Clinical significance of Her-2/neu overexpression in uterine serous carcinoma. Gynecol Oncol 2006; 100: 139-144.
51. Kuhn E, Wu R-C, Wu G, et al. Identification of molecular pathway aberrations in uterine serous carcinoma by genome-wide analyses. J Natl Ca Instit 2012; 104:1503-1513.
52. Konecny GE, Agarwal R, Keeney GA, et al. Claudin-3 and claudin-4 expression in serous papillary, clear-cell, and endometrioid endometrial cancer. Gynecol Oncol 2008; 109:263-269.
53. Santin AD, Sellone S, Marizzoni M, et al. Overexpression of claudin-3 and claudin-4 receptors in uterine serous papillary carcinoma: novel targets for type-specific therapy using Clostridium perfringens enterotoxin (CPE). Cancer 2007; 109:1312-1322.
54. Llaurado M, Ruiz A, Majem B, et al. Molecular bases of endometrial cancer: new roles for actors in the diagnosis and therapy of the disease. Mol Cell Endocrinol 2011; 358:244-255.
55. Goodsell D. The molecular perspective: p53 tumor suppressor. Oncologist 1999; 4:138-139.
56. Attias-Geva Z, Bentov H, Kidron D, et al. p53 regulates insulin-like growth factor-1 receptor gene expression in uterine serous carcinoma and predicts responsiveness toan insulin-like growth-factor-1 receptor-directed targeted therapy. Eur J Cancer 2012; 48:1570-1580.
57. Shih leM, Panuganti PK, Kuo KT, et al. Somatic mutations of PPP2R1A in ovarian and uterine carcinomas. Am J Pathol 2011; 78:1442-1447.
58. Nagendra DC, Burke J, Maxwell GL, et al. PPP2R1A mutations are common in the serous type of endometrial cancer. Mol Carcinogenesis 2011; 51:826-831.
59. Welcker M, Clurman B. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer 2008; 8:83-93.
60. Mao J-H, Kim I-J, Wu D, et al. FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science 2008; 321:1499-1502.
61. Cassia R, Moreno-Bueno G, Rodriguez-Perales S, et al. Cyclin E gene (CCNE) amplification and hCDC4 mutations in endometrial carcinoma. J Pathol 2003; 201:589-595.
62. Paradiso A, Mangia A, Tommasi S. Phosphatidylinositol 3-kinase in breast cancer: where from here? Clin Cancer Res 2007; 13:5988-5990.
63. Hayes MP, Douglas W, Ellenson LH. Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma. Gynecol Oncol 2009; 113:370-373.
64. Oza AM, Elit L, Biagi J, et al. Molecular correlates associated with a phase II study of temsirolimus (CCI-779) in patients with metastatic or recurrent endometrial cancer-NCICIND 160 [abstract]. J Clin Oncol 2006; 24 (18S):3003.
65. Oza AM, Elit L, Provencher D, et al. A phase II study of temsirolimus (CCI-779) in patients with metastatic and/or locally advanced recurrent endometrial cancer previously treated with chemotherapy: NCIC GTC INC 160b [abstract]. J Clin Oncol 2008; 29:3278-3285.
66. Fleming GF, Filiaci VL, Hanjani P, et al. Hormone therapy plus temsirolimus for endometrial carcinoma (EC): aGyencologic Oncology Group trial (#248) [abstract]. J Clin Oncol 2011; 29S:5014.
67. Alvarez E, Brady W, Walker J, et al. Phase II trial of combination bevacizumab ad temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study [abstract]. Gynecol Oncol 2012; 125 (S1):517.
68. Slomovitz BM, Brown J, Johnston TA, et al. A phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma [abstract]. J Clin Oncol 2011; 29S:5012.
69. Mackay H, Welch S, Tsao MS, et al. Phase II study of oral ridaforolimus in patients with metastatic and/or locally advanced recurrent endometrial cancer: NCIC CTG IND 192 [abstract]. J Clin Oncol 2011; 29S:5013.
70. Oza AM, Poveda A, Clamp AR, et al. A randomized phase II trial of ridaforolimus compared with progestin or chemotherapy in female adult patients with advanced endometrial carcinoma [abstract]. J Clin Oncol 2011; 29S:5009.
71. NIH Clinical Trials. A Phase II study to evaluate the efficacy of TKI258 for the treatment of patients with FGFR2 mutated or wild-type advanced and/or metastatic endometrial cancer. http://clinicaltrials.gov/ct2/show/NCT01379534. [Accessed 15 September 2012]
72. Colas E, Pedrola N, Devis L, et al. The EMT signaling pathways in endometrial carcinoma. Clin Transl Oncol 2012; 14:715-720.
73. Gehrig PA, Groben PA, Fowler W, et al. Noninvasive papillary serous carcinoma of the endometrium. Obstet Gynecol 2001; 97:153-157.
74. Holcomb K, Delatorre R, Bader Pedemonte B, et al. E-Cadherin expression in endometrioid, papillary serous, and clear cell carcinoma of the endometrium. Obstet Gynecol 2002; 100:1290-1295.
75. van der Horst PH, Wang Y, Vandenput I, et al. Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer. PLoS One 2012; 7:e30840.
76. Dong P, Kaneuchi M, Watari H, et al. MicroRNA-194 inhibits epithelial to mesenchymal transition of endometrial cancer cells by targeting oncogene BMI-1. Mol Cancer 2011; 10:99.
77. Castilla MA, Moreno-Bueno G, Romero-Pé rez L, et al. Micro-RNA signatures in the epithelial-to-mesenchymal transition in endometrial carcinoma. J Pathol 2011; 223:72-80.
78. Thault S, Valcourt U, Petersen M, et al. Transforming growth factor-b employs HMGA2 to elicit epithelial-mesenchymal transition. J Cell Biol 2006; 174:175-183.
79. McCluggage WG, Connolly LE, McBride HA, et al. HMGA2 is commonly expressed in uterine serous carcinomas and is a useful adjunct to diagnosis. Histopathol 2012; 60:547-553.
80. Lavie O, Ben-Arie A, Segev Y, et al. BRCA germline mutations in women with uterine serous carcinoma-still a debate. Int J Gynecol Cancer 2010; 20:1531-1534.
81. Hornreich G, Beller U, Lavie O, et al. Is uterine serous papillary carcinoma a BRCA1-related disease? Case report and review of the literature. Gynecol Oncol 1999; 75:300-304.
82. Biron-Shental T, Drucker L, Altaras M, et al. High incidence of BRCA1-2 germline mutations, previous breast cancer and familial cancer history in Jewish patients with uterine serous papillary carcinoma. Eur J Surg Oncol 2006; 32:1097-1100.
83. Goshen R, Chu W, Elit W, et al. Is uterine papillary serous adenocarcinoma a manifestation of the hereditary breast-ovarian cancer syndrome? Gynecol Oncol 2000; 79:477-481.
84. Levine D, Lin O, Barakat R, et al. Risk of endometrial carcinoma associated with BRCA mutation. Gynecol Oncol 2001; 80:395-398.
85. Pennington KT, Walsh T, Lee M, et al. BRCA1, TP53, and CHEK2 germline mutations in uterine serous carcinoma. Cancer 2012. doi://10.1002/cncr.27720. [Epub ahead of print]
86. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 1995; 57:1457-1462.
87. Amichay K, Kidron D, Attias-Geva Z, et al. BRCA1 is expressed in uterine serous carcinoma (USC) and controls insulin-like growth factor I receptor (IGF-IR) gene expression in USC cell lines. Int J Gynecol Ca 2012; 22:748-754.
88. Desrichard A, Bidet Yannick, Uhrhammer N, et al. CHEK2 contribution to hereditary breast cancer in non-BRCA families. Breast Ca Res 2011; 13:R119.
89. Growden WB, Rauh-Hain J, Cordon A, et al. Prognostic determinants in patients with stage I uterine papillary serous carcinoma. Int J Gynecol Ca 2012; 22:417-424.
90. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005; 97:1652-1662.
91. Hampbel H, Frankel W, Panescu J, et al. Screening for Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) among endometrial cancer patients. Cancer Res 2006; 66:7810-7817.
92. Meyer LA, Broaddus RR, Lu KH. Endometrial cancer and Lynch syndrome: clinical and pathologic considerations. Cancer Control 2009; 16:14-22.
93. Goodfellow PJ, Buttin BM, Herzog TJ, et al. Prevalence of defective DNA mismatch repair and MSH6 mutation in unselected series of endometrial cancers. Proc Natl Acad Sci USA 2003; 100:12629-12633.
94. Dewdney SB, Kizer NT, Andaya AA, et al. Uterine serous carcinoma: increased familial risk for Lynch-associated malignancies. Cancer Prev Res 2012; 5:435-443.
95. El-Sawhi K, Bellone S, Cocco E, et al. Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201). Mol Cancer Ther 2010; 9:57-66.
96. Varughese J, Cocco E, Bellone S, et al. Uterine serous papillary carcinomas overexpress human trophoblast cell surface marker (Trop-2) and are highly sensitive to immunotherapy with hRS7, a humanized anti-Trop-2 monoclonal antibody. Cancer 2011; 117:3163-3172.
97. Bellone M, Cocco E, Varughese JV, et al. Expression of a-V integrins in uterine serous papillary carcinomas: implications for immunotherapy with intetumumab (CTNO-95), a fully human antagonist anti a-V integrin antibody. Int J Gynecol Cancer 2011; 21:1084-1090.
98. Bellone S, Roque D, Cocco E, et al. Down-regulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitizes uterine serous carcinoma overexpressing HER2/neu to complement and antibodydependent-cell-cytotoxicity in vitro: implications for trastuzumab-based immunotherapy. Br J Cancer 2012; 106:1543-1550.
99. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nature Rev Mol Cell Biol 2001; 2:127-137.
100. Berchuck A, Rodriguez G, Kinney RB, et al. Overexpression of HER2/Neu in endometrial cancer is associated with advanced stage disease. Am J Obstet Gynecol 1991; 164:15-21.
101. Arnould L, Gelly M, Penault-Llorca F, et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer 2006; 94:259-267.
102. Piccart-Gebhart M, Proctor M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 35:1659-1672.
103. Genentech, Inc. Herceptin development timeline. http://www.gene. com/gene/products/information/oncology/herceptin/timeline.html. [Accessed 15 September 2012]
104. Santin AD, Bellone S, Roman JJ, et al. Trastuzumab treatment in patients with advanced or recurrent endometrial carcinoma overexpressing HER2/Neu. Int J Gynaecol Obstet 2008; 102:128-131.
105. Jewell E, Secord AA, Brotherton T, et al. Use of trastuzumab in the treatment of metastatic endometrial cancer. Int J Gynecol Cancer 2006; 16:1370-1373.
106. Villella JA, Cohen S, Smith DH, et al. HER2/Neu overexpression in uterine papillary serous cancers and its possible therapeutic implications. Int J Gynecol Cancer 2006; 16:1897-1902.
107. Fleming GF, Sill MW, Darcy KM, et al. Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: A Gynecologic Oncology Group study. J Clin Oncol 2010; 116:15-20.
108. Santin AD. Letter to the Editor RE: Phase II trial of trastuzumab in women with advanced or recurrent HER2-positive endometrial carcinoma: A Gynecologic Oncology Group Study. Gynecol Oncol 2010; 118:95-96.
109. Todeschini P, Cocco E, Bellone S, et al. HER2/Neu extracellular domain shedding in uterine serous carcinomas: implications for immunotherapy with trastuzumab. Br J Cancer 2011; 105:1176-1182.
110. NIH Clinical Trials. Evaluation of carboplatin/paclitaxel with and without trastuzumab (Herceptin) in uterine serous cancer. http://clinicaltrials. gov/ct2/show/NCT01367002. [Accessed 15 September 2012]
111. Sitohy B, Nagy JA, Dvorak HF. Anti-VEGF/VEGFR therapy for cancer: reassessing the target. Cancer Res 2012; 72:1909-1914.
112. Morotti M, Menada MV, Venturini PL, et al. Bevacizumab in endometrial cancer treatment. Expert Opin Biol Ther 2012; 12:649-658.
113. Kamat AA, Merritt WM, Coffey D, et al. Clinical and biological significance of vascular endothelial growth factor in endometrial cancer. Clin Cancer Res 2007; 13:7487-7495.
114. Hirai M, Nakagawara A, Oosaki T, et al. Expression of vascular endothelial growth factors (VEGF-A/VEGF-1and VEGF-C/VEGF-2) in postmenopausal uterine endometrial carcinoma. Gyneol Oncol 2001; 80:180-188.
115. Mazurek A, Pierzyń ski P, Kuć P, et al. Evaluation of angiogenesis, p-53 tissue protein expression, and serum VEGF in patients with endometrial cancer. Neoplasma 2004; 51:193-197.
116. Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res 2005; 65:671-680.
117. Aghajanian C, Sill MW, Darcy KM, et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2011; 29:2259-2265.
118. NIH Clinical Trials. Evaluation of carboplatin/paclitaxel/bevacizumab in the treatment of advanced stage endometrial carcinoma. http://clinicaltrials. gov/ct2/show/NCT00513786. [Accessed 15 September 2012]
119. NIH Clinical Trials. Paclitaxel, carboplatin, and bevacizumab or paclitaxel, carboplatin, and temsirolimus or ixabepilone, carboplatin, bevacizumab in treating patients with stage III, stage IV, or recurrent endometrial cancer. http://clinicaltrials.gov/ct2/show/NCT00977574. [Accessed 15 September 2012]
120. NIH Clinical Trials. VEGF Trap in treating patients with recurrent or persistent endometrial cancer. http://clinicaltrials.gov/ct2/show/NCT00462826. [Accessed 15 September 2012]
121. McMeekin SD, Filiaci VL, Thigpen JT, et al. The relationship between histology and outcome in advanced and recurrent endometrial cancer patients participating in first-line chemotherapy trials: a Gynecologic Oncology Group study. Gynecol Oncol 2007; 106:16-22.
122. Kavallaris M, Kuo D, Burkhart CA, et al. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific b-tubulin isotypes. J Clin Invest 1997; 100:1282-1298.
123. Magnani M, Ortuso F, Soro S, et al. The bI/bIII-tubulin isoforms and their complexes with antimitotic agents: docking and molecular dynamics studies. FEBS J 2006; 273:3301-3310.
124. Ferlini C, Raspaglio G, Cicchillitti L, et al. Looking at drug resistance mechanisms for microtubule interacting drugs: does TUBB3 work? Cur Cancer Drug Targets 2007; 7:704-712.
125. Ferrandina G, Zannoni GF, Martinelli E, et al. Class III b-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res 2006; 12:2774-2779.
126. Seve P, Isaac S, Trédan O, et al. Expression of class III b-Tubulin is predictive of patient outcome in patients with nonsmall cell lung cancer receiving vinorelbine-based chemotherapy. Clin Cancer Res 2005; 11:5481-5486.
127. Paradiso A, Mangia A, Chiriatti A, et al. Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer. Ann Oncol 2005; 16 (Suppl 4):14-19.
128. Bollag DM, McQueney PA, Zhu J, et al. Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 1995; 55:2325-2333.
129. Paik D, Cocco E, Bellone S, et al. Higher sensitivity to patupilone versus paclitaxel chemotherapy in primary uterine serous papillary carcinoma cell lines with high versus low HER-2/neu expression in vitro. Gynecol Oncol 2010; 119:140-145.
130. Bristol-Meyers Squibb. Ixempra prescribing information. http://www.accessdata. fda.gov/drugsatfda-docs/label/2009/022065s001lbl.pdf. [Accessed 15 September 2012]
131. Dizon DS, Blessing JA, McMeekin DS, et al. Phase II trial of ixabepilone as second-line treatment in advanced endometrial cancer: Gynecologic Oncology Group Trial 129-P. J Clin Oncol 2009; 27:3104-3108.