Emerging therapeutic targets in endometrial cancer

Nature Reviews Clinical Oncology

Volumn 8, Issue 5, 2011, Pages 261-271

  Dedes, Konstantin J ^a   Wetterskog, Daniel ^a   Ashworth, Alan ^a   Kaye, Stan B ^a   Reis Filho, Jorge S ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AFATINIB; AFLIBERCEPT; BEVACIZUMAB; BRIVANIB; CARBOPLATIN; CETUXIMAB; EPHRIN RECEPTOR A2; EPIDERMAL GROWTH FACTOR RECEPTOR; EPITHELIAL CELL ADHESION MOLECULE; ERLOTINIB; EVEROLIMUS; FIBROBLAST GROWTH FACTOR RECEPTOR; GEFITINIB; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MAMMALIAN TARGET OF RAPAMYCIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; PACLITAXEL; PERTUZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RIDAFOROLIMUS; SORAFENIB; SUNITINIB; TEMSIROLIMUS; THALIDOMIDE; TOPOTECAN; TRASTUZUMAB; UNINDEXED DRUG; VASCULOTROPIN;

BREAST CANCER; CANCER CLASSIFICATION; CANCER COMBINATION CHEMOTHERAPY; CANCER HORMONE THERAPY; CANCER SURVIVAL; CARCINOSARCOMA; CLINICAL EFFECTIVENESS; DNA REPAIR; DRUG EFFICACY; DRUG POTENCY; DRUG TARGETING; DRUG TOLERABILITY; ENDOMETRIUM CANCER; ENDOMETRIUM CARCINOMA; GENE EXPRESSION REGULATION; HISTOPATHOLOGY; HUMAN; LOSS OF FUNCTION MUTATION; METASTASIS; MICROSATELLITE INSTABILITY; MOLECULARLY TARGETED THERAPY; MONOTHERAPY; NONHUMAN; PRIORITY JOURNAL; RECURRENT CANCER; REVIEW; SIGNAL TRANSDUCTION; STOMACH CANCER;

ANIMALS; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; ENDOMETRIAL NEOPLASMS; FEMALE; HUMANS; NEOPLASM PROTEINS;

EID: 79955577284     PISSN: 17594774     EISSN: 17594782     Source Type: Journal    
DOI: 10.1038/nrclinonc.2010.216     Document Type: Review

References (139)

1. Jemal, A. Siegel, R., Xu, J. & Ward, E. Cancer statistics, 2010. CA Cancer J. Clin. 60, 277-300 (2010).
2. Plataniotis, G. et al. Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 21 (Suppl. 5), v41-v45 (2010).
3. Surveillance Epidemiology and End Results. SEER Cancer Statistics Review 1975-2007 [online], http://seer.cancer.gov/csr/1975-2007/index.html (2010).
4. Bokhman, J. V. Two pathogenetic types of endometrial carcinoma. Gynecol. Oncol. 15, 10-17 (1983). (Pubitemid 13194678)
5. Hecht, J. L. & Mutter, G. L. Molecular and pathologic aspects of endometrial carcinogenesis. J. Clin. Oncol. 24, 4783-4791 (2006). (Pubitemid 46630943)
6. Risinger, J. I. et al. Microarray analysis reveals distinct gene expression profiles among different histologic types of endometrial cancer. Cancer Res. 63, 6-11 (2003). (Pubitemid 36070410)
7. Lax, S. F., Pizer, E. S., Ronnett, B. M. & Kurman, R. J. 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. Pathol. 29, 924-931 (1998). (Pubitemid 28422040)
8. Fujimoto, T. et al. Endometrioid uterine cancer: histopathological risk factors of local and distant recurrence. Gynecol. Oncol. 112, 342-347 (2009).
9. Lax, S. F., Pizer, E. S., Ronnett, B. M. & Kurman, R. J. Clear cell carcinoma of the endometrium is characterized by a distinctive profile of p53, Ki-67, estrogen, and progesterone receptor expression. Hum. Pathol. 29, 551-558 (1998). (Pubitemid 28272707)
10. Hamilton, C. A. et al. Uterine papillary serous and clear cell carcinomas predict for poorer survival compared to grade 3 endometrioid corpus cancers. Br. J. Cancer 94, 642-646 (2006). (Pubitemid 43361894)
11. Amant, F. et al. Endometrial cancer. Lancet 366, 491-505 (2005). (Pubitemid 41111699)
12. Dutt, A. et al. Drug-sensitive FGFR2 mutations in endometrial carcinoma. Proc. Natl Acad. Sci. USA 105, 8713-8717 (2008). (Pubitemid 351987745)
13. Konecny, G. E. et al. HER2 gene amplification and EGFR expression in a large cohort of surgically staged patients with nonendometrioid (type II) endometrial cancer. Br. J. Cancer 100, 89-95 (2009).
14. Salvesen, H. B. et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc. Natl Acad. Sci. USA 106, 4834-4839 (2009).
15. Dellinger, T. H. & Monk, B. J. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Rev. Anticancer Ther. 9, 905-916 (2009).
16. Greer, B. E. et al. Uterine Neoplasms. Clinical Practice Guidelines in Oncology. J. Natl Compr. Canc. Netw. 7, 498-531 (2009).
17. McMeekin, D. S. 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. 106, 16-22 (2007). (Pubitemid 46898605)
18. Tavassoli, F. A. & Delilee, P. (Eds) Pathology and Genetics of Tumours of the Breast and Female Genital Organs (World Health Organization Classification of Tumours) (IARC Press, Lyon, France, 2003).
19. Creasman, W. T. et al. Carcinoma of the corpus uteri. FIGO 6th Annual Report on the Results of Treatment in Gynecological Cancer. Int. J. Gynaecol. Obstet. 95 (Suppl. 1), S105-S143 (2006).
20. Acharya, S., Hensley, M. L., Montag, A. C. & Fleming, G. F. Rare uterine cancers. Lancet Oncol. 6, 961-971 (2005). (Pubitemid 41685229)
21. Slomovitz, B. M. et al. Uterine papillary serous carcinoma (UPSC): a single institution review of 129 cases. Gynecol. Oncol. 91, 463-469 (2003). (Pubitemid 38388137)
22. Kobel, M. et al. The biological and clinical value of p53 expression in pelvic high-grade serous carcinomas. J. Pathol. 222, 191-198 (2010).
23. McCluggage, W. G. Uterine carcinosarcomas (malignant mixed Mullerian tumors) are metaplastic carcinomas. Int. J. Gynecol. Cancer 12, 687-690 (2002). (Pubitemid 35388035)
24. Maxwell, G. L. et al. Microarray analysis of endometrial carcinomas and mixed mullerian tumors reveals distinct gene expression profiles associated with different histologic types of uterine cancer. Clin. Cancer Res. 11, 4056-4066 (2005). (Pubitemid 40791569)
25. Geyer, F. C. et al. Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas. J. Pathol. 220, 562-573 (2010).
26. Tsuda, H., Yamamoto, K., Inoue, T., Uchiyama, I. & Umesaki, N. The role of p16-cyclin d/CDK-pRb pathway in the tumorigenesis of endometrioid-type endometrial carcinoma. Br. J. Cancer 82, 675-682 (2000). (Pubitemid 30085207)
27. Koul, A., Willen, R., Bendahl, P. O., Nilbert, M. & Borg, A. Distinct sets of gene alterations in endometrial carcinoma implicate alternate modes of tumorigenesis. Cancer 94, 2369-2379 (2002). (Pubitemid 34457118)
28. Suehiro, Y. et al. Aneuploidy predicts outcome in patients with endometrial carcinoma and is related to lack of CDH13 hypermethylation. Clin. Cancer Res. 14, 3354-3361 (2008).
29. Holcomb, K. et al. E-cadherin expression in endometrioid, papillary serous, and clear cell carcinoma of the endometrium. Obstet. Gynecol. 100, 1290-1295 (2002). (Pubitemid 35449197)
30. Moreno-Bueno, G. et al. Abnormalities of E-and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. J. Pathol. 199, 471-478 (2003). (Pubitemid 36411224)
31. Fadare, O. & Zheng, W. Insights into endometrial serous carcinogenesis and progression. Int. J. Clin. Exp. Pathol. 2, 411-432 (2009).
32. Morrison, C. et al. HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients. J. Clin. Oncol. 24, 2376-2385 (2006). (Pubitemid 46630670)
33. Oda, K., Stokoe, D., Taketani, Y. & McCormick, F. High frequency of coexistent mutations of PIK3CA and PTEN genes in endometrial carcinoma. Cancer Res. 65, 10669-10673 (2005). (Pubitemid 41713332)
34. Catasus, L., Gallardo, A., Cuatrecasas, M. & Prat, J. Concomitant PI3K-AKT and p53 alterations in endometrial carcinomas are associated with poor prognosis. Mod. Pathol. 22, 522-529 (2009).
35. Hayes, M. P., Douglas, W. & Ellenson, L. H. Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma. Gynecol. Oncol. 113, 370-373 (2009).
36. Miyake, T. et al. PIK3CA gene mutations and amplifications in uterine cancers, identified by methods that avoid confounding by PIK3CA pseudogene sequences. Cancer Lett. 261, 120-126 (2008).
37. Catasus, L., Gallardo, A., Cuatrecasas, M. & Prat, J. PIK3CA mutations in the kinase domain (exon 20) of uterine endometrial adenocarcinomas are associated with adverse prognostic parameters. Mod. Pathol. 21, 131-139 (2008). (Pubitemid 351172164)
38. Mutter, G. L. et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J. Natl Cancer Inst. 92, 924-930 (2000).
39. Risinger, J. I. et al. PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin. Cancer Res. 4, 3005-3010 (1998). (Pubitemid 29001474)
40. Shoji, K. et al. The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. Br. J. Cancer 101, 145-148 (2009).
41. Kalinsky, K. et al. PIK3CA mutation associates with improved outcome in breast cancer. Clin. Cancer Res. 15, 5049-5059 (2009).
42. Byron, S. A. et al. Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation. Cancer Res. 68, 6902-6907 (2008).
43. Lax, S. F., Kendall, B., Tashiro, H., Slebos, R. J. & Hedrick, L. The frequency of p53, K-ras mutations, and microsatellite instability differs in uterine endometrioid and serous carcinoma: evidence of distinct molecular genetic pathways. Cancer 88, 814-824 (2000). (Pubitemid 30091101)
44. Mackay, H. J. et al. Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: results from studies of the NCIC Clinical Trials Group (NCIC CTG). Eur. J. Cancer 46, 1365-1373 (2010).
45. Kanamori, Y. et al. PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy. Int. J. Cancer 100, 686-689 (2002). (Pubitemid 34832979)
46. Pallares, J. et al. Immunohistochemical analysis of PTEN in endometrial carcinoma: a tissue microarray study with a comparison of four commercial antibodies in correlation with molecular abnormalities. Mod. Pathol. 18, 719-727 (2005). (Pubitemid 40676385)
47. Pollock, P. M. et al. Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. Oncogene 26, 7158-7162 (2007). (Pubitemid 350059681)
48. Turner, N. & Grose, R. Fibroblast growth factor signalling: from development to cancer. Nat. Rev. Cancer 10, 116-129 (2010).
49. Khalifa, M. A., Mannel, R. S., Haraway, S. D., Walker, J. & Min, K. W. Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. Gynecol. Oncol. 53, 84-92 (1994). (Pubitemid 24136907)
50. Livasy, C. A., Reading, F. C., Moore, D. T., Boggess, J. F. & Lininger, R. A. EGFR expression and HER2/neu overexpression/amplification in endometrial carcinosarcoma. Gynecol. Oncol. 100, 101-106 (2006). (Pubitemid 41815057)
51. Jia, L. et al. Endometrial glandular dysplasia with frequent p53 gene mutation: a genetic evidence supporting its precancer nature for endometrial serous carcinoma. Clin. Cancer Res. 14, 2263-2269 (2008). (Pubitemid 351551056)
52. Liggett, W. H. Jr & Sidransky, D. Role of the p16 tumor suppressor gene in cancer. J. Clin. Oncol. 16, 1197-1206 (1998). (Pubitemid 28108758)
53. Ignatov, A. et al. P16 alterations increase the metastatic potential of endometrial carcinoma. Gynecol. Oncol. 111, 365-371 (2008).
54. Salvesen, H. B., Das, S. & Akslen, L. A. Loss of nuclear p16 protein expression is not associated with promoter methylation but defines a subgroup of aggressive endometrial carcinomas with poor prognosis. Clin. Cancer Res. 6, 153-159 (2000). (Pubitemid 30064988)
55. Wong, Y. F. et al. p16INK4 and p15INK4B alterations in primary gynecologic malignancy. Gynecol. Oncol. 65, 319-324 (1997). (Pubitemid 27216948)
56. Stefansson, I. M., Salvesen, H. B. & Akslen, L. A. Prognostic impact of alterations in P-cadherin expression and related cell adhesion markers in endometrial cancer. J. Clin. Oncol. 22, 1242-1252 (2004). (Pubitemid 41079838)
57. Moreno-Bueno, G. et al. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene 21, 7981-7990 (2002). (Pubitemid 35430609)
58. Schlosshauer, P. W., Ellenson, L. H. & Soslow, R. A. Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype. Mod. Pathol. 15, 1032-1037 (2002).
59. Schlosshauer, P. W., Pirog, E. C., Levine, R. L. & Ellenson, L. H. Mutational analysis of the CTNNB1 and APC genes in uterine endometrioid carcinoma. Mod. Pathol. 13, 1066-1071 (2000).
60. Fukuchi, T. et al. Beta-catenin mutation in carcinoma of the uterine endometrium. Cancer Res. 58, 3526-3528 (1998). (Pubitemid 28376543)
61. Jiricny, J. The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. 7, 335-346 (2006).
62. Miturski, R. et al. Mismatch repair genes and microsatellite instability as molecular markers for gynecological cancer detection. Exp. Biol. Med. (Maywood) 227, 579-586 (2002).
63. MacDonald, N. D. et al. Frequency and prognostic impact of microsatellite instability in a large population-based study of endometrial carcinomas. Cancer Res. 60, 1750-1752 (2000). (Pubitemid 30183451)
64. Basil, J. B., Goodfellow, P. J., Rader, J. S., Mutch, D. G. & Herzog, T. J. Clinical significance of microsatellite instability in endometrial carcinoma. Cancer 89, 1758-1764 (2000).
65. Bilbao, C. et al. The relationship between microsatellite instability and PTEN gene mutations in endometrial cancer. Int. J. Cancer 119, 563-570 (2006). (Pubitemid 43955709)
66. Popat, S., Hubner, R. & Houlston, R. S. Systematic review of microsatellite instability and colorectal cancer prognosis. J. Clin. Oncol. 23, 609-618 (2005). (Pubitemid 46224239)
67. Bertagnolli, M. M. et al. Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. J. Clin. Oncol. 27, 1814-1821 (2009).
68. Hewish, M., Lord, C. J., Martin, S. A., Cunningham, D. & Ashworth, A. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nat. Rev. Clin. Oncol. 7, 197-208 (2010).
69. Goodfellow, P. J. Clinicopathologic significance of DNA mismatch repair defects in endometrial cancer: the devil is in the details. Gynecol. Oncol. 113, 151-152 (2009).
70. Black, D. et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J. Clin. Oncol. 24, 1745-1753 (2006). (Pubitemid 46622146)
71. Wik, E. et al. Deoxyribonucleic acid ploidy in endometrial carcinoma: a reproducible and valid prognostic marker in a routine diagnostic setting. Am. J. Obstet. Gynecol. 201, 603.e1-603.e7 (2009).
72. Lukes, A. S. et al. Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer. Cancer 73, 2380-2385 (1994). (Pubitemid 24129123)
73. Lebeau, A. et al. Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma and its precursor lesions. J. Pathol. 216, 151-157 (2008).
74. Tan, D. S., Lambros, M. B., Marchio, C. & Reis-Filho, J. S. ESR1 amplification in endometrial carcinomas: hope or hyperbole? J. Pathol. 216, 271-274 (2008).
75. Reis-Filho, J. S. et al. ESR1 gene amplification in breast cancer: a common phenomenon? Nat. Genet. 40, 809-810 (2008). (Pubitemid 351913662)
76. Jongen, V. et al. Expression of estrogen receptor-alpha and -beta and progesterone receptor-A and -B in a large cohort of patients with endometrioid endometrial cancer. Gynecol. Oncol. 112, 537-542 (2009).
77. Kohler, M. F. et al. Mutational analysis of the estrogen-receptor gene in endometrial carcinoma. Obstet. Gynecol. 86, 33-37 (1995).
78. Arnett-Mansfield, R. L. et al. Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium. Cancer Res. 61, 4576-4582 (2001). (Pubitemid 32685792)
79. Thomson, A. W. & Woo, J. Immunosuppressive properties of FK-506 and rapamycin. Lancet 2, 443-444 (1989). (Pubitemid 19195978)
80. Stallone, G. et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N. Engl. J. Med. 352, 1317-1323 (2005). (Pubitemid 40411498)
81. Dancey, J. mTOR signaling and drug development in cancer. Nat. Rev. Clin. Oncol. 7, 209-219 (2010).
82. Faivre, S., Kroemer, G. & Raymond, E. Current development of mTOR inhibitors as anticancer agents. Nat. Rev. Drug Discov. 5, 671-688 (2006). (Pubitemid 44151605)
83. Oza, A. M. 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 CTG IND 160b [abstract]. J. Clin. Oncol. 26 (Suppl.), a5516 (2008).
84. Oza, A. M. et al. Phase I study of temsirolimus (CCI-779), carboplatin, and paclitaxel in patients (pts) with advanced solid tumors: NCIC CTG IND 179 [abstract]. J. Clin. Oncol. 27 (Suppl. 15), a3558 (2009).
85. Temkin, S. M., Yamada, S. D. & Fleming, G. F. A phase I study of weekly temsirolimus and topotecan in the treatment of advanced and/or recurrent gynecologic malignancies. Gynecol. Oncol. 117, 473-476 (2010).
86. Colombo, N. et al. A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer [abstract]. J. Clin. Oncol. 25 (18 Suppl.), a5516 (2007).
87. Fetterly, G. J. et al. Pharmacokinetics of oral deforolimus (AP23573, MK-8669) [abstract]. J. Clin. Oncol. 26 (Suppl.), a14555 (2008).
88. Slomovitz, B. M. et al. A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma. Cancer 116, 5415-5419 (2010).
89. Hay, N. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8, 179-183 (2005). (Pubitemid 41317589)
90. Bader, A. G., Kang, S. & Vogt, P. K. Cancer-specific mutations in PIK3CA are oncogenic in vivo. Proc. Natl Acad. Sci. USA 103, 1475-1479 (2006). (Pubitemid 43191190)
91. Noh, W. C. et al. Determinants of rapamycin sensitivity in breast cancer cells. Clin. Cancer Res. 10, 1013-1023 (2004).
92. Brachmann, S. M. et al. Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells. Proc. Natl Acad. Sci. USA 106, 22299-22304 (2009).
93. Raynaud, F. I. et al. Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer Res. 67, 5840-5850 (2007). (Pubitemid 46985018)
94. Fan, Q. W. et al. A dual PI3 kinase/mTOR inhibitor reveals emergent efficacy in glioma. Cancer Cell 9, 341-349 (2006).
95. Raynaud, F. I. et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol Cancer Ther. 8, 1725-1738 (2009).
96. Niikura, H. et al. Prognostic value of epidermal growth factor receptor expression in endometrioid endometrial carcinoma. Hum. Pathol. 26, 892-896 (1995).
97. Scambia, G. et al. Significance of epidermal growth factor receptor expression in primary human endometrial cancer. Int. J. Cancer 56, 26-30 (1994). (Pubitemid 24044788)
98. Oza, A. M. et al. Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148. J. Clin. Oncol. 26, 4319-4325 (2008).
99. Slomovitz, B. et al. Phase II study of cetuximab (Erbitux) in patients with progressive or recurrent endometrial cancer [abstract]. Gynecol. Oncol. 116 (Suppl.1), S13 (2010).
100. Rosell, R. et al. Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med. 361, 958-967 (2009).
101. Zhu, C. Q. et al. Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J. Clin. Oncol. 26, 4268-4275 (2008).
102. Burtness, B. et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J. Clin. Oncol. 23, 8646-8654 (2005). (Pubitemid 46211507)
103. Bardelli, A. & Siena, S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J. Clin. Oncol. 28, 1254-1261 (2010).
104. Villella, J. A., Cohen, S., Smith, D. H., Hibshoosh, H. & Hershman, D. HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications. Int. J. Gynecol. Cancer 16, 1897-1902 (2006). (Pubitemid 44470053)
105. Jewell, E., Secord, A. A., Brotherton, T. & Berchuck, A. Use of trastuzumab in the treatment of metastatic endometrial cancer. Int. J. Gynecol. Cancer 16, 1370-1373 (2006). (Pubitemid 43886771)
106. Fleming, G. F. et al. Phase II trial of trastuzumab in women with advanced or recurrent, HER2-positive endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol. Oncol. 116, 15-20 (2010).
107. Cobleigh, M. A. et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J. Clin. Oncol. 17, 2639-2648 (1999). (Pubitemid 29415219)
108. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783-792 (2001). (Pubitemid 32222155)
109. Bang, Y. J. et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376, 687-697 (2010).
110. Konecny, G. E. et al. Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human endometrial cancer cells. Br. J. Cancer 98, 1076-1084 (2008). (Pubitemid 351399811)
111. El-Sahwi, K. et al. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. Br. J. Cancer 102, 134-143 (2010).
112. Sivridis, E. et al. Angiogenic co-operation of VEGF and stromal cell TP in endometrial carcinomas. J. Pathol. 196, 416-422 (2002). (Pubitemid 34262853)
113. Salvesen, H. B., Iversen, O. E. & Akslen, L. A. Prognostic significance of angiogenesis and Ki-67, p53, and p21 expression: a population-based endometrial carcinoma study. J. Clin. Oncol. 17, 1382-1390 (1999). (Pubitemid 29220843)
114. Stefansson, I. M., Salvesen, H. B. & Akslen, L. A. Vascular proliferation is important for clinical progress of endometrial cancer. Cancer Res. 66, 3303-3309 (2006).
115. Kamat, A. A. et al. Clinical and biological significance of vascular endothelial growth factor in endometrial cancer. Clin. Cancer Res. 13, 7487-7495 (2007).
116. McMeekin, D. S. et al. A phase II trial of thalidomide in patients with refractory endometrial cancer and correlation with angiogenesis biomarkers: a Gynecologic Oncology Group study. Gynecol. Oncol. 105, 508-516 (2007). (Pubitemid 46591977)
117. Aghajanian, C. et al. A phase II evaluation of bevacizumab in the treatment of recurrent or persistent endometrial cancer: A Gynecologic Oncology Group (GOG) Study [abstract]. J. Clin. Oncol. 27 (Suppl. 15), a5531 (2009).
118. Nimeiri, H. S. et al. Sorafenib (SOR) in patients (pts) with advanced/recurrent uterine carcinoma (UCA) or carcinosarcoma (CS): A phase II trial of the University of Chicago, PMH, and California Phase II Consortia [abstract]. J. Clin. Oncol. 26 (Suppl.), a5585 (2008).
119. Correa, R. et al. A phase II study of sunitinib in recurrent or metastatic endometrial carcinoma: a trial of the Princess Margaret Hospital, The University of Chicago, and California Cancer Phase II Consortia [abstract]. J. Clin. Oncol. 28 (Suppl. 15), a5038 (2010).
120. Pasquale, E. B. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nat. Rev. Cancer 10, 165-180 (2010).
121. Lee, J. W. et al. EphA2 immunoconjugate as molecularly targeted chemotherapy for ovarian carcinoma. J. Natl Cancer Inst. 101, 1193-1205 (2009).
122. Thaker, P. H. et al. EphA2 expression is associated with aggressive features in ovarian carcinoma. Clin. Cancer Res. 10, 5145-5150 (2004). (Pubitemid 39099789)
123. Kamat, A. A. et al. EphA2 overexpression is associated with lack of hormone receptor expression and poor outcome in endometrial cancer. Cancer 115, 2684-2692 (2009).
124. Lee, J. W. et al. EphA2 targeted chemotherapy using an antibody drug conjugate in endometrial carcinoma. Clin. Cancer Res. 16, 2562-2570 (2010).
125. Santin, A. D. 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 92, 1561-1573 (2005). (Pubitemid 40705026)
126. El-Sahwi, K. et al. Overexpression of EpCAM in uterine serous papillary carcinoma: implications for EpCAM-specific immunotherapy with human monoclonal antibody adecatumumab (MT201). Mol Cancer Ther. 9, 57-66 (2010).
127. Carmeliet, P. et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394, 485-490 (1998). (Pubitemid 28373960)
128. Hockel, M. et al. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res. 56, 4509-4515 (1996). (Pubitemid 26330463)
129. Schindl, M. et al. Overexpression of hypoxia-inducible factor 1alpha is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin. Cancer Res. 8, 1831-1837 (2002). (Pubitemid 34633742)
130. Pansare, V. et al. Increased expression of hypoxia-inducible factor 1alpha in type I and type II endometrial carcinomas. Mod. Pathol. 20, 35-43 (2007). (Pubitemid 44967948)
131. Kato, H. et al. Induction of human endometrial cancer cell senescence through modulation of HIF-1alpha activity by EGLN1. Int. J. Cancer 118, 1144-1153 (2006). (Pubitemid 43185600)
132. Schwartz, D. L. et al. The selective hypoxia inducible factor-1 inhibitor PX-478 provides in vivo radiosensitization through tumor stromal effects. Mol. Cancer Ther. 8, 947-958 (2009).
133. Shen, W. H. et al. Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128, 157-170 (2007). (Pubitemid 46048887)
134. McEllin, B. et al. PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res. 70, 5457-5464 (2010).
135. Mendes-Pereira, A. M. et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol. Med. 1, 315-322 (2009).
136. Dedes, K. J. et al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors. Sci. Transl. Med. 2, 53ra75 (2010).
137. Ang, J. E. et al. A feasibility study of sequential doublet chemotherapy comprising carboplatin-doxorubicin and carboplatin-paclitaxel for advanced endometrial adenocarcinoma and carcinosarcoma. Ann. Oncol. 20, 1787-1793 (2009).
138. Cirisano, F. D. Jr et al. Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma. Gynecol. Oncol. 74, 385-394 (1999). (Pubitemid 29439878)
139. Matthews, R. P. et al. Papillary serous and clear cell type lead to poor prognosis of endometrial carcinoma in black women. Gynecol. Oncol. 65, 206-212 (1997). (Pubitemid 27216929)