Molecular target therapies in endometrial cancer: From the basic research to the clinic

Gynecological Endocrinology

Volumn 24, Issue 5, 2008, Pages 239-249

  Gadducci, Angiolo ^a   Tana, Roberta ^a   Cosio, Stefania ^a   Fanucchi, Antonio ^a   Genazzani, Andrea Riccardo ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

Clostridium perfringens enterotoxin; Endometrial cancer; Gefitinib; Imatinib; Mammalian target of rapamycin; Trastuzumab; Tyrosine kinase inhibitors

Indexed keywords

AP 23573; BEVACIZUMAB; CAPECITABINE; CCI 799; CISPLATIN; CLAUDIN 3; CLAUDIN 4; DOCETAXEL; DOXORUBICIN; ENTEROTOXIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERLOTINIB; EVEROLIMUS; GEFITINIB; GRANULOCYTE COLONY STIMULATING FACTOR; IMATINIB; LAPATINIB; MAMMALIAN TARGET OF RAPAMYCIN; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN TYROSINE KINASE INHIBITOR; RAPAMYCIN DERIVATIVE; TAXANE DERIVATIVE; TENSIROLIMUS; TRASTUZUMAB;

CANCER RADIOTHERAPY; CLINICAL TRIAL; CLOSTRIDIUM PERFRINGENS; DRUG DOSE ESCALATION; DRUG MECHANISM; DRUG RESPONSE; ENDOMETRIUM CANCER; FATIGUE; HUMAN; MOLECULAR THERAPY; NEUTROPENIA; PRIORITY JOURNAL; PROTEIN EXPRESSION; RASH; REVIEW; SIGNAL TRANSDUCTION; UTERUS CARCINOMA;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CARCINOMA, ENDOMETRIOID; CYSTADENOCARCINOMA, PAPILLARY; DRUG DELIVERY SYSTEMS; ENDOMETRIAL NEOPLASMS; ENTEROTOXINS; FEMALE; HUMANS; PROTEIN KINASES; PTEN PHOSPHOHYDROLASE; RECEPTOR, ERBB-2; SIGNAL TRANSDUCTION; SIROLIMUS;

EID: 45949095023     PISSN: 09513590     EISSN: 14730766     Source Type: Journal    
DOI: 10.1080/09513590801953556     Document Type: Review

References (147)

1. Bakkum-Gamez JN, Gonzalez-Bosquet J, Laack NN, Mariani A, Dowdy SC. Current issues in the management of endometrial cancer. Mayo Clin Proc 2008;83:97-112.
2. Sherman ME, Kurman RJ. Evolving concepts in endometrial carcinogenesis: importance of DNA repair and deregulated growth. Hum Pathol 1998;29:1035-1038.
3. Matias-Guiu X, Catasus L, Bussaglia E, Lagarda H, Garcia A, Pons C, Muñoz J, Argüelles R, Machin P, Prat J. Molecular pathology of endometrial hyperplasia and carcinoma. Hum Pathol 2001;32:569-577.
4. Koul A, Willén R, Bendahl PO, Nilbert M, Borg A. Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis. Cancer 2002;94:2369-2379.
5. Lax SF. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 2004;444:213-223.
6. Mutch DG, Powell MA, Mallon MA, Goodfellow PJ. RAS/RAF mutation and defective DNA mismatch repair in endometrial cancers. Am J Obstet Gynecol 2004;190:935-942.
7. Pappa KI, Choleza M, Markaki S, Giannikaki E, Kyroudi A, Vlachos G, Voulgaris Z, Anagnou NP. Consistent absence of BRAF mutations in cervical and endometrial cancer despite KRAS mutation status. Gynecol Oncol 2006;100:596-600.
8. Abal M, Planaguma J, Gil-Moreno A, Monge M, Gonzalez M, Baro T, Garcia A, Castellvi J, Ramon Y, Cajal S, et al. Molecular pathology of endometrial carcinoma: transcriptional signature in endometrioid tumors. Histol Histopathol 2006;21:197-204.
9. Maggino T, Romagnolo C, Zola P, Sartori E, Landoni F, Gadducci A. An analysis of approaches to the treatment of endometrial cancer in western Europe: a CTF study. Eur J Cancer 1995;31A:1993-1997.
10. Maggino T, Romagnolo C, Landoni F, Sartori E, Zola P, Gadducci A. An analysis of approaches to the management of endometrial cancer in North America: a CTF study. Gynecol Oncol 1998;68:274-279.
11. Kilgore LC, Partridge EE, Alvarez RD, Austin JM, Shingleton HM, Noojin F 3rd, Conner W. Adenocarcinoma of the endometrium: survival comparisons of patients with and without pelvic node sampling. Gynecol Oncol 1995; 56:29-33.
12. Carey MS, O'Connell GJ, Johanson CR, Goodyear MD, Murphy KJ, Daya DM, Schepansky A, Peloquin A, Lumsden BJ. Good outcome associated with a standardized treatment protocol using selective postoperative radiation in patients with clinical stage I adenocarcinoma of the endometrium. Gynecol Oncol 1995;57:138-144.
13. Eltabbakh GH, Piver MS, Hempling RE, Shin KH. Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling: report of a prospective trial. Int J Radiat Oncol Biol Phys 1997;38:373-380.
14. Trimble EL, Kosary C, Park RC. Lymph node sampling and survival in endometrial cancer. Gynecol Oncol 1998;71:340-343.
15. Mariani A, Webb MJ, Keeney GL, Haddock MG, Calori G, Podratz KC. Low-risk corpus cancer: is lymphadenectomy or radiotherapy necessary? Am J Obstet Gynecol 2000;182: 1506-1519.
16. Cragun JM, Havrilesky LJ, Calingaert B, Synan I, Secord AA, Soper JT, Clarke-Pearson DL, Berchuck A. Retrospective analysis of selective lymphadenectomy in apparent early-stage endometrial cancer. J Clin Oncol 2005;23:3668-3675.
17. Mariani A, Dowdy SC, Cliby WA, Haddock MG, Keeney GL, Lesnick TG, Podratz KC. Efficacy of systematic lymphadenectomy and adjuvant radiotherapy in node-positive endometrial cancer patients. Gynecol Oncol 2006; 101:200-208.
18. Chan JK, Kapp DS. Role of complete lymphadenectomy in endometrioid uterine cancer. Lancet Oncol 2007;8: 831-841.
19. Fujimoto T, Nanjyo H, Nakamura A, Yokoyama Y, Takano T, Shoji T, Nakahara K, Yamada H, Mizunuma H, Yaegashi N, et al. Para-aortic lymphadenectomy may improve disease-related survival in patients with multipositive pelvic lymph node stage IIIc endometrial cancer. Gynecol Oncol 2007;107:253-259.
20. Tozzi R, Malur S, Koehler C, Schneider A. Laparoscopy versus laparotomy in endometrial cancer: first analysis of survival of a randomized prospective study. J Minim Invasive Gynecol 2005;12:130-136.
21. Schlaerth AC, Abu-Rustum NR. Role of minimally invasive surgery in gynecologic cancers. Oncologist 2006;11:895-901.
22. Janda M, Gebski V, Forder P, Jackson D, Williams G, Obermair A. Total laparoscopic versus open surgery for stage 1 endometrial cancer: the LACE randomized controlled trial. Contemp Clin Trials 2006;27:353-363.
23. Cirisano FD Jr, Robboy SJ, Dodge RK, Bentley RC, Krigman HR, Synan IS, Soper JT, Clarke-Pearson DL. Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometriod carcinoma. Gynecol Oncol 1999;74:385-394.
24. Bristow RE, Duska LR, Montz FJ. The role of cytoreductive surgery in the management of stage IV uterine papillary serous carcinoma. Gynecol Oncol 2001;81:92-99.
25. Chan JK, Loizzi V, Youssef M, Osann K, Rutgers J, Vasilev SA, Berman ML. Significance of comprehensive surgical staging in noninvasive papillary serous carcinoma of the endometrium. Gynecol Oncol 2003;90:181-185.
26. Slomovitz BM, Burke TW, Eifel PJ, Ramondetta LM, Silva EG, Jhingran A, Oh JC, Atkinson EN, Broaddus RR, Gershenson DM, Lu KH. Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases. Gynecol Oncol 2003;91:463-469.
27. Maggino T, Gadducci A. Uterine papillary serous carcinoma. In: Bosze P, editor. Endometrial cancer. European practice in gynaecology and obstetrics series, Amsterdam: Elsevier; 2003. pp 205-212.
28. Schwartz PE. The management of serous papillary uterine cancer. Curr Opin Oncol 2006;18:494-499.
29. Havrilesky LJ, Secord AA, Bae-Jump V, Ayeni T, Calingaert B, Clarke-Pearson DL, Berchuck A, Gehrig PA. Outcomes in surgical stage I uterine papillary serous carcinoma. Gynecol Oncol 2007;105:677-682.
30. Johnson N, Cornes P. Survival and recurrent disease after postoperative radiotherapy for early endometrial cancer: systematic review and meta-analysis. BJOG 2007;114: 1313-1320.
31. Jolly S, Vargas C, Kumar T, Weiner S, Brabbins D, Chen P, Floyd W, Martinez AA. Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer. Gynecol Oncol 2005;97:887-892.
32. Rankins NC, Secord AA, Jewell E, Havrilesky LJ, Soper JT, Myers E. Cost-effectiveness of adjuvant radiotherapy in intermediate risk endometrial cancer. Gynecol Oncol 2007; 106:388-393.
33. Creutzberg CL. PORTEC2: Postoperative Radiation Therapy for Endometrial Carcinoma - a multicenter randomised phase III trial comparing external beam radiation and vaginal brachytherapy [Internet]. Leiden (The Netherlands): Leiden University Medical Centre; [2003]. Available from: http://www.clinicalresearch. nl/portec2/PORTEC-2
34. Corn BW, Lanciano RM, Greven KM, Schultz DJ, Reisinger SA, Stafford PM, Hanks GE. Endometrial cancer with para-aortic adenopathy: patterns of failure and opportunities for cure. Int J Radiat Oncol Biol Phys 1992;24:223-227.
35. Rose PG, Cha SD, Tak WK, Fitzgerald T, Reale F, Hunter RE. Radiation therapy for surgically proven para-aortic node metastasis in endometrial carcinoma. Int J Radiat Oncol Biol Phys 1992;24:229-233.
36. De Palo G, Mangioni C, Periti P, Del Vecchio M, Marubini E. Treatment of FIGO (1971) stage I endometrial carcinoma with intensive surgery, radiotherapy and hormonotherapy according to pathological prognostic groups. Long-term results of a randomised multicentre study. Eur J Cancer 1993;29A:1133-1140.
37. Rotman M, Aziz H, Boronow R. Insights in para-aortic radiation therapy for endometrial carcinoma. Int J Radiat Oncol Biol Phys 1993;26:711-712.
38. Mundt AJ, McBride R, Rotmensch J, Waggoner SE, Yamada SD, Connell PP. Significant pelvic recurrence in high risk pathologic stage I-IV endometrial carcinoma patients after adjuvant chemotherapy alone: implications for adjuvant radiation therapy. Int J Radiat Oncol Biol Phys 2001;50:1145-1153.
39. Maggi R, Lissoni A, Spina F, Melpignano M, Zola P, Favalli G, Colombo A, Fossati R. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomized trial. Br J Cancer 2006;95:266-271.
40. Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA. Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 2006;24:36-44.
41. Kodama J, Seki N, Hiramatsu Y. Chemotherapy for high-risk early-stage endometrial cancer. Curr Opin Obstet Gynecol 2007;19:42-47.
42. Hiura M, Nogawa T, Matsumoto T, Yokoyama T, Shiroyama Y, Wroblewski J, Hirata E. Long-term survival in patients with para-aortic lymph node metastasis with systematic retroperitoneal lymphadenectomy followed by adjuvant chemotherapy in endometrial carcinoma 2007 ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2007;25(Suppl):16011(abstract)
43. Susumu N, Sagae S, Udagawa Y, Niwa K, Kuramoto H, Satoh S, Kudo R. Japanese Gynecologic Oncology Group. Randomized phase III trial of pelvic radiotherapy versus cisplatin-based combined chemotherapy in patients with intermediate- and high-risk endometrial cancer: a Japanese Gynecologic Oncology Group study. Gynecol Oncol 2008; 108:226-233.
44. Onda T, Yoshikawa H, Mizutani K, Mishima M, Yokota H, Nagano H, Ozaki Y, Murakami A, Ueda K, Taketani Y. Treatment of node-positive endometrial cancer with complete node dissection, chemotherapy and radiation therapy. Br J Cancer 1997;75:1836-1841.
45. Greven K, Winter K, Underhill K, Fontenesci J, Cooper J, Burke T. Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer. Gynecol Oncol 2006;103:155-159.
46. Mangili G, De Marzi P, Beatrice S, Rabaiotti E, Viganò R, Frigerio L, Gentile C, Fazio F. Paclitaxel and concomitant radiotherapy in high-risk endometrial cancer patients: preliminary findings. BMC Cancer 2006;6:198.
47. Lupe K, Kwon J, D'Souza D, Gawlik C, Stitt L, Whiston F, Nascu P, Wong E, Carey MS. Adjuvant paclitaxel and carboplatin chemotherapy with involved field radiation in advanced endometrial cancer: a sequential approach. Int J Radiat Oncol Biol Phys 2007;67:110-116.
48. Bancher-Todesca D, Neunteufel W, Williams KE, Prainsack D, Breitenecker G, Friedlander ML, Hacker NF. Influence of postoperative treatment on survival in patients with uterine papillary serous carcinoma. Gynecol Oncol 1998;71:344-347.
49. Santin AD, Bellone S, O'Brien TJ, Pecorelli S, Cannon MJ, Roman JJ. Current treatment options for endometrial cancer. Expert Rev Anticancer Ther 2004;4:679-689.
50. Kelly MG, O'Malley DM, Hui P, McAlpine J, Yu H, Rutherford TJ, Azodi M, Schwartz PE. 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.
51. Duska LR, Berkowitz R, Matulonis U, Muto M, Goodman A, McIntyre JF, Klein A, Atkinson T, Seiden MV, Campos S. A pilot trial of TAC (paclitaxel, doxorubicin, and carboplatin) chemotherapy with filgastrim (r-metHuG-CSF) support followed by radiotherapy in patients with "high-risk" endometrial cancer. Gynecol Oncol 2005;96: 198-203.
52. Huh WK. What is the correct management of stage IUPSC? Int J Gynecol Cancer 2005;15:405-406.
53. Dietrich CS, 3rd Modesitt SC, DePriest PD, Ueland FR, Wilder J, Reedy MB, Pavlik EJ, Kryscio R, Cibull M, Giesler J, et al. The efficacy of adjuvant platinum-based chemotherapy in stage I uterine papillary serous carcinoma (UPSC). Gynecol Oncol 2005;99:557-563.
54. Hamilton CA, Liou WS, Osann K, Berman ML, Husain A, Teng NN, Kapp DS, Chan JK. Impact of adjuvant therapy on survival of patients with early-stage uterine papillary serous carcinoma. Int J Radiat Oncol Biol Phys 2005; 63:839-844.
55. Low JS, Wong EH, Tan HS, Yap SP, Chua EJ, Sethi VK, Soh LT, Low J, Tay EH, Chew SH. Adjuvant sequential chemotherapy and radiotherapy in uterine papillary serous carcinoma. Gynecol Oncol 2005;97:171-177.
56. Steed H, Manchul L, Rosen B, Fyles A, Lockwood G, Laframboise S, Murphy J, Milosevic M, Chapman W, Oza AM. Uterine papillary serous carcinoma: evaluation of multimodality treatment with abdominopelvic radiotherapy and chemotherapy. Int J Gynecol Cancer 2006;16:278-285.
57. Thomas MB, Mariani A, Cliby WA, Keeney GA, Podratz KC, Dowdy SC. Role of systematic lymphadenectomy and adjuvant therapy in stage I uterine papillary serous carcinoma. Gynecol Oncol 2007;107:186-189.
58. Viswanathan A, Horick N, Tanaka C, Campos S, Matulonis U, Berkowitz R. Chemotherapy and radiation therapy in UPSC. J Clin Oncoll, 2007. ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S, 2007: 5535.
59. Fields AL, Einstein MH, Novetsky AP, Gebb J, Goldberg GL. Pilot phase II trial of radiation 'sandwiched' between combination paclitaxel/platinum chemotherapy in patients with uterine papillary serous carcinoma (UPSC). Gynecol Oncol 2008;108:201-206.
60. Thigpen JT, Brady MF, Alvarez RD, Adelson MD, Homesley HD, Manetta A, Soper JT, Given FT. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 1999; 17:1736-1744.
61. Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer 2007;17:964-978.
62. Lai C, Huang H. The role of hormones for the treatment of endometrial hyperplasia and endometrial cancer. Curr Opin Obstet Gynecol 2006;18:29-34.
63. Gadducci A, Cosio S, Genazzani AR. Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: hormonal therapy, chemotherapy and molecularly targeted therapies. Crit Rev Oncol Hematol 2006;58:242-256.
64. Pectasides D, Pectasides E, Economopoulos T. Systemic therapy in metastatic or recurrent endometrial cancer. Cancer Treat Rev 2007;33:177-190.
65. Garrett A, Quinn MA. Hormonal therapies and gynaecological cancers. Best Pract Res Clin Obstet Gynaecol 2007 Sep 18; [Epub ahead of print].
66. Aapro MS, van Wijk FH, Bolis G, Chevallier B, van der Burg ME, Poveda A, de Oliveira CF, Tumolo S, Scotto di Palumbo V, Piccart M, et al. European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol 2003;14:441-448.
67. Thigpen JT, Brady MF, Homesley HD, Malfetano J, DuBeshter B, Burger RA, Liao S. 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.
68. van Wijk FH, Lhommé C, Bolis G, Scotto di Palumbo V, Tumolo S, Nooij M, de Oliveira CF, Vermorken JB. European Organization for Research and Treatment of Cancer. Gynaecological Cancer Group. Phase II study of carboplatin in patients with advanced or recurrent endometrial carcinoma. A trial of the EORTC Gynaecological Cancer Group. Eur J Cancer 2003;39:78-85.
69. Fleming GF, Brunetto VL, Cella D, Look KY, Reid GC, Munkarah AR, Kline R, Burger RA, Goodman A, Burks RT. 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.
70. Akram T, Maseelall P, Fanning J. Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. Am J Obstet Gynecol 2005;192:1365-1367.
71. McMeekin DS, Filiaci VL, Thigpen JT, Gallion HH, Fleming GF, Rodgers WH. Gynecologic Oncology Group study. 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.
72. Secord AA, Havrilesky LJ, Carney ME, Soper JT, Clarke-Pearson DL, Rodriguez GC, Berchuck A. Weekly low-dose paclitaxel and carboplatin in the treatment of advanced or recurrent cervical and endometrial cancer. Int J Clin Oncol 2007;12:31-36.
73. Pignata S, Scambia G, Pisano C, Breda E, Di Maio M, Greggi S, Ferrandina G, Lorusso D, Zagonel V, Febbraro A, et al. Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies Group. A multicentre phase II study of carboplatin plus pegylated liposomal doxorubicin as first-line chemotherapy for patients with advanced or recurrent endometrial carcinoma: the END-1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) group. Br J Cancer 2007;96:1639-1643.
74. Mountzios G, Bamias A, Voulgaris Z, Rodolakis A, Vlahos G, Gourgoulis G, Papaiakovou EE, Giannopoulos A. Prognostic factors in patients treated with taxane-based chemotherapy for recurrent or metastatic endometrial cancer: proposal for a new prognostic model. Gynecol Oncol 2008;108:130-135.
75. Kew FM, Roberts AP, Cruickshank DJ. The role of routine follow-up after gynecological malignancy. Int J Gynecol Cancer 2005;15:413-419.
76. Albitar L, Laidler LL, Abdallah R, Leslie KK. Regulation of signaling phosphoproteins by epidermal growth factor and Iressa (ZD1839) in human endometrial cancer cells that model type I and II tumors. Mol Cancer Ther 2005;4: 1891-1899.
77. De Luca A, Carotenuto A, Rachiglio A, Gallo M, Maiello MR, Aldinucci D, Pinto A, Normanno N. The role of the EGFR signaling in tumor microenvironment. J Cell Physiol 2008;214:559-567.
78. Kitao K, Yoshida S, Kennedy S, Takemura N, Sugimoto M, Deguchi M, Ohara N, Maruo T. Epidermal growth factor receptor and human epidermal growth factor receptor 2 gene polymorphisms in endometrial cancer in a Japanese population. Reprod Sci 2007;14:349-357.
79. Khalifa MA, Mannel RS, Haraway SD, Walker J, Min KW. Expression of EGFR, HER2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. Gynecol Oncol 1994;53:84-92.
80. Reinartz JJ, George E, Lindgren BR, Niehans GA. Expression of p53, transforming growth factor α, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival. Hum Pathol 1994;25:1075-1083.
81. Scambia G, Benedetti Panici P, Ferrandina G, Battaglia F, Distefano M, D'Andrea G, De Vincenzo R, Maneschi F, Ranelletti FO, Mancuso S. Significance of epidermal growth factor receptor expression in primary human endometrial cancer. Int J Cancer 1994;56:26-30.
82. Niikura H, Sasano H, Matsunaga G, Watanabe K, Ito K, Sato S, Yajima A. Prognostic value of epidermal growth factor receptor expression in endometrioid endometrial carcinoma. Hum Pathol 1995;26:892-896.
83. Yokoyama Y, Takahashi Y, Hashimoto M, Morishita S, Tamaya T. Immunohistochemical study of estradiol, epidermal growth factor, transforming growth factor α and epidermal growth factor receptor in endometrial neoplasia. Jpn J Clin Oncol 1996;26:411-416.
84. Nagai N, Oshita T, Fujii T, Kioka H, Katsube Y, Ohama K. Prospective analysis of DNA ploidy, proliferative index and epidermal growth factor receptor as prognostic factors for pretreated uterine cancer. Oncol Rep 2000;7:551-559.
85. Brys M, Semczuk A, Rechberger T, Krajewska WM. Expression of erbB-1 and erbB-2 genes in normal and pathological human endometrium. Oncol Rep 2007;18:261-265.
86. Niikura H, Sasano H, Kaga K, Sato S, Yajima A. Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium. Hum Pathol 1996;27:282-289.
87. Dai D, Litman ES, Schonteich E, Leslie KK. Progesterone regulation of activating protein-1 transcriptional activity: a possible mechanism of progesterone inhibition of endometrial cancer cell growth. J Steroid Biochem Mol Biol 2003; 87:123-131.
88. Davies S, Dai D, Wolf DM, Leslie KK. Immunomodulatory and transcriptional effects of progesterone through progesterone A and B receptors in Hec50co poorly differentiated endometrial cancer cells. J Soc Gynecol Investig 2004;11: 494-499.
89. Davies S, Dai D, Feldman I, Pickett G, Leslie KK. Identification of a novel mechanism of NF-κB inactivation by progesterone through progesterone receptors in Hec50co poorly differentiated endometrial cancer cells: induction of A20 and ABIN-2. Gynecol Oncol 2004;94:463-470.
90. Dai D, Albitar L, Nguyen T, Laidler LL, Singh M, Leslie KK. A therapeutic model for advanced endometrial cancer: systemic progestin in combination with local adenoviral-mediated progesterone receptor expression. Mol Cancer Ther 2005;4:169-175.
91. Davies S, Dai D, Pickett G, Leslie KK. Gene regulation profiles by progesterone and dexamethasone in human endometrial cancer Ishikawa H cells. Gynecol Oncol 2006;101:62-70.
92. Albitar L, Carter MB, Davies S, Leslie KK. Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Gynecol Oncol 2007; 106:94-104.
93. Honda R, Tanaka H. Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 1997;420:25-27.
94. Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, et al. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy. Proc Natl Acad Sci USA 2006;103:1888-1893.
95. Zhao S, Chen X, Lu X, Yu Y, Feng Y. Epidermal growth factor receptor signaling enhanced by long-term medroxyprogesterone acetate treatment in endometrial carcinoma. Gynecol Oncol 2007;105:45-54.
96. Leslie KK, Laidler L, Albitar L, Davies S, Holmes A, Nguyen T, Bolnick J, Dai D. Tyrosine kinase inhibitors in endometrial cancer. Int J Gynecol Cancer 2005;15:409-411.
97. Jasa KV, Fyles A, Elit L, Hoskins PJ, Biagi J, Dubuc-Lissoir J, Matthews S, Dancey J, Eisenhauer E, Oza AM. Phase II study of erlotinib (OSI 774) in women with recurrent or metastatic endometrial cancer: NCIC CTG IND-148. 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition) J Clin Oncol 2004;22(Suppl):5019.
98. Moy B, Goss PE. Lapatinib-associated toxicity and practical management recommendations. Oncologist 2007;12:756-765.
99. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. Oncologist 2007;12:756-765.
100. Prat J, Oliva E, Lerma E, Vaquero M, Matías-Guiu X. Uterine papillary serous adenocarcinoma. A 10-case study of p53 and c-erbB-2 expression and DNA content. Cancer 1994;74:1778-1783.
101. Santin AD, Bellone S, Gokden M, Palmieri M, Dunn D, Agha J, Roman JJ, Hutchins L, Pecorelli S, O'Brien T, et al. Overexpression of HER-2/neu in uterine serous papillary cancer. Clin Cancer Res 2002;8:1271-1279.
102. Villella JA, Cohen S, Smith DH, Hibshoosh H, Hershman D. HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications. Int J Gynecol Cancer 2006;16:1897-1902.
103. Santin AD, Zhan F, Bellone S, Palmieri M, Cane S, Gokden M, Roman JJ, O'Brien TJ, Tian E, Cannon MJ, et al. Discrimination between uterine serous papillary carcinomas and ovarian serous papillary tumors by gene expression profiling. Br J Cancer 2004;90:1814-1824.
104. Slomovitz BM, Broaddus RR, Burke TW, Sneige N, Soliman PT, Wu W, Sun CC, Munsell MF, Gershenson DM, Lu KH. Her-2/neu overexpression and amplification in uterine papillary serous carcinoma. J Clin Oncol 2004;22:3126-3132.
105. Santin AD, Zhan F, Cane' S, Bellone S, Palmieri M, Thomas M, Burnett A, Roman JJ, Cannon MJ, Shaughnessy J Jr, et al. Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy. Br J Cancer 2005;92:1561-1573.
106. Santin AD, Bellone S, Siegel ER, Palmieri M, Thomas M, Cannon MJ, Kay HH, Roman JJ, Burnett A, Pecorelli S. Racial differences in the overexpression of epidermal growth factor type II receptor (HER2/neu): a major prognostic indicator in uterine serous papillary cancer. Am J Obstet Gynecol 2005;192:813-818.
107. Lukes AS, Kohler MF, Pieper CF, Kerns BJ, Bentley R, Rodriguez GC, Soper JT, Clarke-Pearson DL, Bast RC Jr, Berchuck A. Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer. Cancer 1994;73:2380-2385.
108. Capdeville R, Silberman S, Dimitrijevic S. Imatinib: the first 3 years. Eur J Cancer 2002;38(Suppl 5):S77-S82.
109. Slomovitz BM, Broaddus RR, Schmandt R, Wu W, Oh JC, Ramondetta LM, Burke TW, Gershenson DM, Lu KH. Expression of imatinib mesylate-targeted kinases in endometrial carcinoma. Gynecol Oncol 2004;95:32-36.
110. Slomovitz BM, Ramondetta LM, Johnston T, Lu KH, Broaddus RR, Muller P, Iyer RB, Burke TW, Gershenson DM, Wolf J. A phase I study of imatinib mesylate and paclitaxel in patients with advanced (stage IIIC/IV) or recurrent uterine papillary serous carcinoma (UPSC) 2007 ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2007;25(Suppl):16025.
111. Chang F, Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, Franklin RA, McCubrey JA. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 2003;1:590-603.
112. McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, Bertrand FE, Navolanic PM, Terrian DM, Franklin RA, D'Assoro AB, et al. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. Adv Enzyme Regul 2006;46:249-279.
113. Jastrzebski K, Hannan KM, Tchoubrieva EB, Hannan RD, Pearson RB. Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function. Growth Factors 2007;25: 209-226.
114. 1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability. J Biol Chem 1998;273: 14424-14429.
115. De Benedetti A. Graff JR. eIF-4E expression and its role in malignancies and metastases. Oncogene 2004;23:3189-3199.
116. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol 2004; 22:2954-2963.
117. Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, Li J, Parsons R, Ellenson LH. Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 1997;57: 3935-3940.
118. Risinger JI, Hayes K, Maxwell GL, Carney ME, Dodge RK, Barrett JC, Berchuck A. PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res 1998;4:3005-3010.
119. Lin WM, Forgacs E, Warshal DP, Yeh IT, Martin JS, Ashfaq R, Muller CY. Loss of heterozygosity and mutational analysis of the PTEN/MMAC1 gene in synchronous endometrial and ovarian carcinomas. Clin Cancer Res 1998;4:2577-2583.
120. Bussaglia E, del Rio E, Matias-Guiu X, Prat J. PTEN mutations in endometrial carcinomas: a molecular and clinicopathologic analysis of 38 cases. Hum Pathol 2000; 31:312-317.
121. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JP, Lees JA, Weng LP, Eng C. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000;92:924-930.
122. An HJ, Lee YH, Cho NH, Shim JY, Kim JY, Lee C, Kim SJ. Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27. Histopathology 2002;41:437-445.
123. Terakawa N, Kanamori Y, Yoshida S. Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endocr Relat Cancer 2003;10:203-208.
124. Slomovitz BM, Wu W, Broaddus RR, Soliman PT, Wolf J, Sun CC, Bodurka DC, Gershenson DM, Lu KH. mTOR inhibition is a rational target for the treatment of endometrial cancer. 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition), J Clin Oncol 2004;22(Suppl):5076.
125. Dutcher JP. Mammalian target of rapamycin inhibition. Clin Cancer Res 2004;10:6382S-6387S.
126. Dudkin L, Dilling MB, Cheshire PJ, Harwood FC, Hollingshead M, Arbuck SG, Travis R, Sausville EA, Houghton PJ. Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Clin Cancer Res 2001;7:1758-1764.
127. Peralba JM, DeGraffenried L, Friedrichs W, Fulcher L, Grünwald V, Weiss G, Hidalgo M. Pharmacodynamic evaluation of CCI-779, an inhibitor of mTOR, in cancer patients. Clin Cancer Res 2003;9:2887-2892.
128. Oza AM, Elit L, Biagi J, Chapman W, Tsao M, Hedley D, Hansen C, Dancey J, Eisenhauer E. Molecular correlates associated with a phase II study of tensirolimus (CCI-779) in patients with metastatic or recurrent endometrial cancer - NCIC IND 160. 2006 ASCO Annual Meeting Proceedings Part I. J Clin Oncol 2006;24(Suppl):3003.
129. Mita MM, Mita A, Rowinski EK. Mammalian target of rapamycin: a new molecular target for breast cancer. Clin Breast Cancer 2003;4:126-137.
130. Boulay A, Zumstein-Mecker S, Stephan C, Beuvink I, Zilbermann F, Haller R, Tobler S, Heusser C, O'Reilly T, Stolz B, et al. Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res 2004; 64:252-261.
131. Wolf J, Slomovitz BM. Novel biologic therapies for the treatment of endometrial cancer. Int J Gynecol Cancer 2005; 15:411.
132. Dancey JE. Inhibitors of the mammalian target of rapamycin. Expert Opin Investig Drugs 2005;14:313-328.
133. Colombo N, McMeekin S, Schwartz P, Kostka J, Sessa C, Gehrig P, Holloway R, Braly P,Matei D, Einstein M. A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer. 2007 ASCO Annual Meeting Proceedings Part I, J Clin Oncol 2007;25(Suppl): 5516.
134. Santin AD, Bellone S, Marizzoni M, Palmieri M, Siegel ER, McKenney JK, Hennings L, Comper F, Bandiera E, Pecorelli S. Overexpression of claudin-3 and claudin-4 receptors in uterine serous papillary carcinoma: novel targets for a type-specific therapy using Clostridium perfringens enterotoxin (CPE). Cancer 2007;109:1312-1322.
135. Michl P, Buchholz M, Rolke M, Kunsch S, Löhr M, McClane B, Tsukita S, Leder G, Adler G, Gress TM. Claudin-4: a new target for pancreatic cancer treatment using Clostridium perfringens enterotoxin. Gastroenterology 2001; 121:678-684.
136. Santin AD, Bellone S, Siegel ER, McKenney JK, Thomas M, Roman JJ, Burnett A, Tognon G, Bandiera E, Pecorelli S. Overexpression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in uterine carcinosarcomas. Clin Cancer Res 2007;13:3339-3346.
137. Hirai M, Nakagawara A, Oosaki T, Hayashi Y, Hirono M, Yoshihara T. Expression of vascular endothelial growth factors (VEGF-A/VEGF-1 and VEGF-C/VEGF-2) in postmenopausal uterine endometrial carcinoma. Gynecol Oncol 2001;80:181-188.
138. Holland CM, Day K, Evans A, Smith SK. Expression of the VEGF and angiopoietin genes in endometrial atypical hyperplasia and endometrial cancer. Br J Cancer 2003; 89:891-898.
139. Kamat AA, Merritt WM, Coffey D, Lin YG, Patel PR, Broaddus R, Nugent E, Han LY, Landen CN, Jr, Spannuth WA, et al. Clinical and biological significance of vascular endothelial growth factor in endometrial cancer. Clin Cancer Res 2007;13:7487-7495.
140. Wright JD, Powell MA, Rader JS, Mutch DG, Gibb RK. Bevacizumab therapy in patients with recurrent uterine neoplasms. Anticancer Res 2007;27:3525-3528.
141. Dinh P, de Azambuja E, Piccart-Gebhart MJ. Trastuzumab for early breast cancer: current status and future directions. Clin Adv Hematol Oncol 2007;5:707-717.
142. Palandri F, Iacobucci I, Martinelli G, Amabile M, Poerio A, Testoni N, Soverini S, Castagnetti F, De Vivo A, Breccia M, et al. GIMEMA Working Party on CML. Long-term outcome of complete cytogenetic responders after imatinib 400 mg in late chronic phase, philadelphia-positive chronic myeloid leukemia: the GIMEMA Working Party of CML. J Clin Oncol 2008;26:106-111.
143. Trent JC, Lazar AJ, Zhang W. Molecular approaches to resolve diagnostic dilemmas: the case of gastrointestinal stromal tumor and leiomyosarcoma. Future Oncol 2007; 3:629-637.
144. Benson AB, 3rd. New approaches to assessing and treating early-stage colon and rectal cancers: cooperative group strategies for assessing optimal approaches in early-stage disease. Clin Cancer Res 2007;13:6913s-6920s.
145. Klein B, Gottfried M. Targeted agents to improve treatment results in colon cancer: bevacizumab and cetuximab. J BUON 2007;12(Suppl 1):S127-S136.
146. Samlowski WE, Vogelzang NJ. Emerging drugs for the treatment of metastatic renal cancer. Expert Opin Emerg Drugs 2007;12:605-618.
147. Cerezo L, Cárdenes H, Michael H. Molecular alterations in the pathogenesis of endometrial adenocarcinoma. Therapeutic implications. Clin Transl Oncol 2006;8:231-241.