382
Views
20
CrossRef citations to date
0
Altmetric
Reviews

An update on the current pharmacotherapy for endometrial cancer

, , , &
Pages 489-499 | Received 26 Jun 2015, Accepted 30 Nov 2015, Published online: 23 Dec 2015

References

  • Eifel PJ. Treatment of endometrial cancer. Pelvic cancer surgery. London: Springer; 2015. p. 315–325.
  • Sheikh MA, Althouse AD, Freese KE, et al. USA endometrial cancer projections to 2030: should we be concerned? Future Oncol. Future Medicine; 2014;10:2561–2568.
  • Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. Wiley Online Library; 2014;64:9–29.
  • Editorial. Adamkeiwicz on the nature and treatment of cancer. JAMA. 1893;XX:399–402.
  • Boldt HJ. The treatment of cancer of the uterus when too far advanced for cure by extirpation of the uterus. JAMA. American Medical Association; 1909;LIII:1883–1887.
  • Clark JG. Results obtained by the use of radium in the treatment of cancer of the uterus: at the University of Pennsylvania Hospital. Ann Surg. 1916;64:602–61.2.
  • Bowing HH, Fricke RE. Results obtained in the treatment of carcinoma of the cervix uteri with radium and roentgen rays from 1915 to 1924, inclusive. Radiology. 1930;14:211–216.
  • Kelley RM, Baker WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961;264:216–222.
  • Cohen CJ. Treatment problems in endometrial cancer. Clin Obstet Gynecol. 1967;10:625–640.
  • Phillips TJ, Progestogens O. Adenocarcinoma of the uterus. BJOG. Blackwell Publishing Ltd; 1966;73:487–489.
  • Bruckner HW, Deppe G. Combination chemotherapy of advanced endometrial adenocarcinoma with adriamycin, cyclophosphamide, 5-fluorouracil, and medroxyprogesterone acetate. Obstet Gynecol. 1977;50:10s–12s.
  • Seski JC, Edwards CL, Herson J, et al. Cisplatin chemotherapy for disseminated endometrial cancer. Obstet Gynecol. Journals.Lww.Com; 1982;59:225–228.
  • Thigpen T, Vance RB, Balducci L, et al. Chemotherapy in the management of advanced or recurrent cervical and endometrial carcinoma. Cancer. 1981;48:658–665.
  • Ball HG, Blessing JA, Lentz SS, et al. A phase II trial of paclitaxel in patients with advanced or recurrent adenocarcinoma of the endometrium: a Gynecologic Oncology Group study. Gynecol Oncol. Elsevier; 1996;62:278–281.
  • Hendrickson M, Ross J, Eifel P, et al. Uterine papillary serous carcinoma: a highly malignant form of endometrial adenocarcinoma. Am J Surg Pathol. 1982;6:93–108.
  • Deligdisch L, Cohen CJ. Histologic correlates and virulence implications of endometrial carcinoma associated with adenomatous hyperplasia. Cancer. Wiley Online Library; 1985;56:1452–1455.
  • Emons G, Fleckenstein G, Hinney B, et al. Hormonal interactions in endometrial cancer. Endocr Relat Cancer. 2000;7:227–242.
  • Bakkum-Gamez JN, Mariani A, Dowdy SC, et al. Efficacy of contemporary chemotherapy in stage IIIC endometrial cancer: a histologic dichotomy. Gynecol Oncol. 2014;132:578–584.
  • AlHilli MM, Mariani A, Bakkum-Gamez JN, et al. Risk-scoring models for individualized prediction of overall survival in low-grade and high-grade endometrial cancer. Gynecol Oncol. 2014;133:485–493.
  • Kurman RJ, Visvanathan K, Shih I-M. Bokhman’s dualistic model of endometrial carcinoma. Revisited. Gynecol Oncol. 2013;129:271–272.
  • 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.
  • Brinton LA, Felix AS, McMeekin DS, et al. Etiologic heterogeneity in endometrial cancer: evidence from a Gynecologic Oncology Group trial. Gynecol Oncol. 2013;129:277–284.
  • Zannoni GF, Vellone VG, Arena V, et al. Does high-grade endometrioid carcinoma (grade 3 FIGO) belong to type I or type II endometrial cancer? A clinical–pathological and immunohistochemical study. Virchows Arch. Springer-Verlag; 2010;457:27–34.
  • Bogani G, Liu MC, Dowdy SC, et al. Detection of circulating tumor cells in high-risk endometrial cancer. Anticancer Res. 2015;35:683–687.
  • Stringer-Reasor E, Fleming G, Tsoref D, et al. Chemotherapy and/or targeted therapies for advanced endometrial cancer: time to rethink? Controversies in the management of gynecological cancers. London: Springer; 2014. p. 59–68.
  • Sherman ME. Theories of endometrial carcinogenesis: a multidisciplinary approach. Mod Pathol. 2000;13:295–308.
  • Hecht JL, Mutter GL. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol. 2006;24:4783–4791.
  • Black JD, English DP, Roque DM, et al. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer. Womens Health. 2014;10:45–57.
  • Oshita T, Shigemasa K, Nagai N, et al. p27, cyclin E, and CDK2 expression in normal and cancerous endometrium. Int J Oncol. 2002. DOI:10.3892/ijo.21.4.737.
  • Santin AD, Bellone S, Marizzoni M, et al. 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. 2007/02/28 Ed. 2007;109:1312–1322.
  • Black JD, Lopez S, Cocco E, et al. Clostridium perfringens enterotoxin (CPE) and CPE-binding domain (c-CPE) for the detection and treatment of gynecologic cancers. Toxins. 2015;7:1116–1125.
  • Morin PJ. Claudin proteins in human cancer: promising new targets for diagnosis and therapy. Cancer Res. 2005;65:9603–9606.
  • Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67–73.
  • Creasman WT, Morrow CP, Bundy BN, et al. Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study. Cancer. 1987;60:2035–2041.
  • Burke WM, Orr J, Leitao M, et al., et al.; SGO Clinical Practice Endometrial Cancer Working Group. Endometrial cancer: a review and current management strategies: part II. Gynecol Oncol. 2014;134:393–402.
  • Gunderson CC, Fader AN, Carson KA, et al. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: a systematic review. Gynecol Oncol. 2012;125:477–482.
  • Gallos ID, Yap J, Rajkhowa M, et al. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012;207:266.e1–12.
  • Thigpen JT, Brady MF, Alvarez RD, et al. 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.
  • Fleming GF, Filiaci VL, Marzullo B, et al. Temsirolimus with or without megestrol acetate and tamoxifen for endometrial cancer: a gynecologic oncology group study. Gynecol Oncol. Elsevier; 2014;132:585–592.
  • Lee W-L, Lee F-K, Su W-H, et al. Hormone therapy for younger patients with endometrial cancer. Taiwan J Obstet Gynecol. 2012;51:495–505.
  • Niwa K, Tagami K, Lian Z, et al. Outcome of fertility-preserving treatment in young women with endometrial carcinomas. BJOG. 2005;112:317–320.
  • Bogani G, Cromi A, Serati M, et al. Chemotherapy reduces para-aortic node recurrences in endometrial cancer with positive pelvic and unknown para-aortic nodes. Int J Gynecol Cancer. 2015;25:263–268.
  • Alvarez Secord A, Havrilesky LJ, Bae-Jump V, et al. The role of multi-modality adjuvant chemotherapy and radiation in women with advanced stage endometrial cancer. Gynecol Oncol. 2007;107:285–291.
  • 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.
  • Aapro MS, Van Wijk FH, Bolis G, et al. Doxorubicin versus doxorubicin and cisplatin in endometrial carcinoma: definitive results of a randomised study (55872) by the EORTC Gynaecological Cancer Group. Ann Oncol. Eur Soc Med Oncology. 2003;14:441–448.
  • 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.
  • Miller D, Filiaci V, Fleming G, et al. Late-breaking abstract 1: randomized phase III noninferiority trial of first line chemotherapy for metastatic or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecologic Oncology. 2012;125:771.
  • Goldfinger M, Diaz I, Muggia F. Systemic treatment of endometrial cancer: what is doxorubicin’s role?. J Clin Oncol. 2014;32:2181–2182.
  • Taylor NP, Powell MA. Therapeutic modalities in early-stage uterine papillary serous carcinomas, carcinosarcomas, clear-cell and mixed histology carcinomas. Uterine cancer. New York (NY): Humana Press; 2009. p. 193–216.
  • Cantrell LA, Blank SV, Duska LR. Uterine carcinosarcoma: a review of the literature. Gynecol Oncol. 2015;137:581–588.
  • Bansal N, Yendluri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2009;16:8–13.
  • Salvesen HB, Carter SL, Mannelqvist M, et al. Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation. Proc Natl Acad Sci U S A. 2009;106:4834–4839.
  • 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.
  • Kanamori Y, Kigawa J, Itamochi H, et al. Correlation between loss of PTEN expression and Akt phosphorylation in endometrial carcinoma. Clin Cancer Res. 2001;7:892–895.
  • Marshall G, Howard Z, Dry J, et al. Benefits of mTOR kinase targeting in oncology: pre-clinical evidence with AZD8055. Biochem Soc Trans. 2011;39:456–459.
  • Chresta CM, Davies BR, Hickson I, et al. AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity. Cancer Res. 2010;70:288–298.
  • Sini P, James D, Chresta C, et al. Simultaneous inhibition of mTORC1 and mTORC2 by mTOR kinase inhibitor AZD8055 induces autophagy and cell death in cancer cells. Autophagy. 2010;6:553–554.
  • Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997;275:1943–1947.
  • Dedes KJ, Wetterskog D, Mendes-Pereira AM, et al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors. Sci Transl Med. 2010;2:53ra75.
  • McEllin B, Camacho CV, Mukherjee 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. 2010;70:5457–5464.
  • Mendes Pereira AM, Martin SA, Brough R, et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med. EMBO Press; 2009;1:315–322.
  • Forster MD, Dedes KJ, Sandhu S, et al. Treatment with olaparib in a patient with PTEN-deficient endometrioid endometrial cancer. Nat Rev Clin Oncol. 2011;8:302–306.
  • Gelmon KA, Hirte HW, Robidoux A, et al. Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J Clin Oncol 2010;28(Suppl. 15):3002. ASCO Annual Meeting Proceedings.
  • Miyabe I, Kunkel TA, Carr AM. The major roles of DNA polymerases epsilon and delta at the eukaryotic replication fork are evolutionarily conserved. PLoS Genet. 2011;7:e1002407.
  • Colombo N, McMeekin S, Schwartz P, et al. A phase II trial of the mTOR inhibitor AP23573 as a single agent in advanced endometrial cancer. ASCO Meet Abstr. 2007;25:5516.
  • Meng B, Hoang LN, McIntyre JB, et al. POLE exonuclease domain mutation predicts long progression-free survival in grade 3 endometrioid carcinoma of the endometrium. Gynecol Oncol. 2014;134:15–19.
  • Santin AD, Bellone S, Centritto F, et al. Improved survival of patients with hypermutation in uterine serous carcinoma. Gynecol Oncol Rep. 2015;12:3–4.
  • Bellone S, Centritto F, Black J, et al. Polymerase ε (POLE) ultra-mutated tumors induce robust tumor-specific CD4+ T cell responses in endometrial cancer patients. Gynecol Oncol. 2015. DOI:10.1016/j.ygyno.2015.04.027.
  • Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.
  • Hari M, Yang H, Zeng C, et al. Expression of class III beta-tubulin reduces microtubule assembly and confers resistance to paclitaxel. Cell Motil Cytoskeleton. 2003;56:45–56.
  • 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.
  • Vitolo MI, Boggs AE, Whipple RA, et al. Loss of PTEN induces microtentacles through PI3K-independent activation of cofilin. Oncogene. 2013;32:2200–2210.
  • 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.
  • Roque DM, Ratner ES, Silasi D-A, et al. Weekly ixabepilone with or without biweekly bevacizumab in the treatment of recurrent or persistent uterine and ovarian/primary peritoneal/fallopian tube cancers: a retrospective review. Gynecol Oncol. 2015;137:392–400.
  • Reyes HD, Thiel KW, Carlson MJ, et al. Comprehensive profiling of EGFR/HER receptors for personalized treatment of gynecologic cancers. Mol Diagn Ther. 2014;18:137–151.
  • Dedes KJ, Wetterskog D, Ashworth A, et al. Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol. 2011;8:261–271.
  • Leslie KK, Sill MW, Lankes HA, et al. Lapatinib and potential prognostic value of EGFR mutations in a Gynecologic Oncology Group phase II trial of persistent or recurrent endometrial cancer. Gynecol Oncol. 2012;127:345–350.
  • Dong P, Xu Z, Jia N, et al. Elevated expression of p53 gain-of-function mutation R175H in endometrial cancer cells can increase the invasive phenotypes by activation of the EGFR/PI3K/AKT pathway. Mol Cancer. 2009;8:103.
  • Leslie KK, Sill MW, Fischer E, et al. A phase II evaluation of gefitinib in the treatment of persistent or recurrent endometrial cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 2013;129:486–494.
  • Oza AM, Eisenhauer EA, Elit L, et al. Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148. J Clin Oncol. 2008;26:4319–4325.
  • Guidi AJ, Abu-Jawdeh G, Tognazzi K, et al. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in endometrial carcinoma. Cancer. 1996;78:454–460.
  • Doldi N, Bassan M, Gulisano M, et al. Vascular endothelial growth factor messenger ribonucleic acid expression in human ovarian and endometrial cancer. Gynecol Endocrinol. 1996;10:375–382.
  • Wang J, Taylor A, Showeil R, et al. Expression profiling and significance of VEGF-A, VEGFR2, VEGFR3 and related proteins in endometrial carcinoma. Cytokine. 2014;68:94–100.
  • Saarelainen SK, Staff S, Peltonen N, et al. Endoglin, VEGF, and its receptors in predicting metastases in endometrial carcinoma. Tumour Biol. 2014;35:4651–4657.
  • Dobrzycka B, Mackowiak-Matejczyk B, Kinalski M, et al. Pretreatment serum levels of bFGF and VEGF and its clinical significance in endometrial carcinoma. Gynecol Oncol. 2013;128:454–460.
  • Powell MA, Sill MW, Goodfellow PJ, et al. A phase II trial of brivanib in recurrent or persistent endometrial cancer: a gynecologic oncology group study. Int J Gynecol Cancer. 2012;22:s3.
  • Gadducci A, Sergiampietri C, Guiggi I. Antiangiogenic agents in advanced, persistent or recurrent endometrial cancer: a novel treatment option. Gynecol Endocrinol. 2013;29:811–816.
  • 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.
  • Alvarez EA, Brady WE, Walker JL, et al. Phase II trial of combination bevacizumab and temsirolimus in the treatment of recurrent or persistent endometrial carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2013;129:22–27.
  • Simpkins F, Drake R, Escobar PF, et al. A phase II trial of paclitaxel, carboplatin, and bevacizumab in advanced and recurrent endometrial carcinoma (EMCA). Gynecol Oncol. 2015;136:240–245.
  • Aghajanian C, Filiaci VL, Dizon DS, et al. A randomized phase II study of paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus and ixabepilone/carboplatin/bevacizumab as initial therapy for measurable stage III or IVA, stage IVB or recurrent endometrial cancer, GOG-86P. J Clin Oncol. 2015;33(Suppl. 15). ASCO Annual Meeting Proceedings. Abstract no. 5500.
  • Stelloo E, Bosse T, Nout RA, et al. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol. 2015. DOI:10.1038/modpathol.2015.43.
  • Zhao S, Choi M, Overton JD, et al. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma. Proc Natl Acad Sci U S A. 2013;110:2916–2921.
  • Fabre C, Gobbi M, Ezzili C, et al. Clinical study of the novel cyclin-dependent kinase inhibitor dinaciclib in combination with rituximab in relapsed/refractory chronic lymphocytic leukemia patients. Cancer Chemother Pharmacol. 2014;74:1057–1064.
  • Kumar SK, LaPlant B, Chng WJ, et al. Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood. 2015;125:443–448.
  • Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16:25–35.
  • Kallioniemi OP, Kallioniemi A, Kurisu W, et al. ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc Natl Acad Sci U S A. 1992;89:5321–5325.
  • Graus-Porta D, Beerli RR, Daly JM, et al. ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling. Embo J. 1997;16:1647–1655.
  • Roskoski R Jr. ErbB/HER protein-tyrosine kinases: structures and small molecule inhibitors. Pharmacol Res. 2014;87:42–59.
  • Llauradó M, Ruiz A, Majem B, et al. Molecular bases of endometrial cancer: new roles for new actors in the diagnosis and the therapy of the disease. Mol Cell Endocrinol. 2012;358:244–255.
  • Teplinsky E, Muggia F. Targeting HER2 in ovarian and uterine cancers: challenges and future directions. Gynecol Oncol. 2014;135:364–370.
  • Buza N, Roque DM, Santin AD. HER2/ neu in endometrial cancer: a promising therapeutic target with diagnostic challenges. Arch Pathol Lab Med. 2014;138. DOI:10.5858/arpa.2012-0416-ra.
  • Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–1672.
  • Jelovac D, Emens LA. HER2-directed therapy for metastatic breast cancer. Oncology. 2013;27:166–175.
  • 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.
  • 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.
  • Villella JA, Cohen S, Smith DH, et al. HER-2/neu overexpression in uterine papillary serous cancers and its possible therapeutic implications. Int J Gynecol Cancer. 2006;16:1897–1902.
  • Nagumo Y, Sims AH, Muir M, et al. Trastuzumab and pertuzumab produce changes in morphology and estrogen receptor signaling in ovarian cancer xenografts revealing new treatment. Clin Cancer Res. AACR; 2011. Available from: http://clincancerres.aacrjournals.org/content/17/13/4451.short
  • El-Sahwi K, Bellone S, Cocco E, et al. In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma. Br J Cancer; 2010;102(1):134–143.
  • Mullen P, Cameron DA, Hasmann M, et al. Sensitivity to pertuzumab (2C4) in ovarian cancer models: cross-talk with estrogen receptor signaling. Mol Cancer Ther. 2007;6:93–100.
  • Kim JW, Kim H-P, Im S-A, et al. The growth inhibitory effect of lapatinib, a dual inhibitor of EGFR and HER2 tyrosine kinase, in gastric cancer cell lines. Cancer Lett. 2008;272:296–306.
  • Groeneweg JW, Hernandez SF, Byron VF, et al. Dual HER2 targeting impedes growth of HER2 gene-amplified uterine serous carcinoma xenografts. Clin Cancer Res. 2014;20:6517–6528.
  • Bloom J, Pagano M. Deregulated degradation of the cdk inhibitor p27 and malignant transformation. Semin Cancer Biol. 2003;13. DOI:10.1016/s1044-579x(02)00098-6.
  • Pagano M, Tam S, Theodoras A, et al. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science. 1995;269. DOI:10.1126/science.7624798.
  • Sherr CJ, Roberts JM. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 1999;13:1501–1512.
  • Lahav-Baratz S. Decreased level of the cell cycle regulator p27 and increased level of its ubiquitin ligase Skp2 in endometrial carcinoma but not in normal secretory or in hyperstimulated endometrium. Mol Hum Reprod. 2004;10. DOI:10.1093/molehr/gah084.
  • Miyamoto T, Horiuchi A, Kashima H, et al. Inverse correlation between Skp2 and p27Kip1 in normal endometrium and endometrial carcinoma. Gynecol Endocrinol. 2009. DOI:10.1080/09513590903215482.
  • Lecanda J, Parekh TV, Gama P, et al. Transforming growth factor-beta, estrogen, and progesterone converge on the regulation of p27Kip1 in the normal and malignant endometrium. Cancer Res. 2007;67:1007–1018.
  • Chu IM, Hengst L, Slingerland JM. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer. 2008;8. DOI:10.1038/nrc2347.
  • Kamata Y, Watanabe J, Nishimura Y, et al. High expression of skp2 correlates with poor prognosis in endometrial endometrioid adenocarcinoma. J Cancer Res Clin Oncol. 2005;131. DOI:10.1007/s00432-005-0671-2.
  • Wander SA, Zhao D, Slingerland JM. p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies. Clin Cancer Res. 2010;17. DOI:10.1158/1078-0432.ccr-10-0752.
  • Davidovich S, Ben-Izhak O, Shapira M, et al. Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer. Breast Cancer Res. 2008;10. DOI:10.1186/bcr2122.
  • Huang KT, Pavlides SC, Lecanda J, et al. Estrogen and progesterone regulate p27kip1 levels via the ubiquitin-proteasome system: pathogenic and therapeutic implications for endometrial cancer. PLoS One. 2012;7(9):e46072.
  • Di Cristofano A, Ellenson LH. Endometrial carcinoma. Annu Rev Pathol: Mech Dis. annualreviews.org; 2007. Available from: http://www.annualreviews.org/doi/abs/10.1146/annurev.pathol.2.010506.091905
  • Ellenson LH, Wu T-C. Focus on endometrial and cervical cancer. Cancer Cell. 2004;5. DOI:10.1016/j.ccr.2004.05.029.
  • Watanabe J, Watanabe K, Jobo T, et al. Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma. Int J Gynecol Cancer. 2006;16(Suppl 1):452–457.
  • Shiozawa T, Horiuchi A, Kato K, et al. Up-regulation of p27Kip1 by progestins is involved in the growth suppression of the normal and malignant human endometrial glandular cells. Endocrinology. 2001;142:4182–4188.
  • An H-J, Lee Y-H, Cho N-H, et al. Alteration of PTEN expression in endometrial carcinoma is associated with down-regulation of cyclin-dependent kinase inhibitor, p27. Histopathology. 2002;41:437–445.
  • Mamillapalli R, Gavrilova N, Mihaylova VT, et al. PTEN regulates the ubiquitin-dependent degradation of the CDK inhibitor p27(KIP1) through the ubiquitin E3 ligase SCF(SKP2). Curr Biol. 2001;11:263–267.
  • Hao B, Zheng N, Schulman BA, et al. Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase. Mol Cell. 2005;20:9–19.
  • Cardozo T, Pagano M. Wrenches in the works: drug discovery targeting the SCF ubiquitin ligase and APC/C complexes. BMC Biochem. 2007;8(Suppl 1):S9.
  • Wu L, Grigoryan AV, Li Y, et al. Specific small molecule inhibitors of Skp2-mediated p27 degradation. Chem Biol. 2012;19:1515–1524.
  • Pavlides SC, Huang K-T, Reid DA, et al. Inhibitors of SCF-Skp2/Cks1 E3 ligase block estrogen-induced growth stimulation and degradation of nuclear p27kip1: therapeutic potential for endometrial cancer. Endocrinology. 2013;154:4030–4045.
  • Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383:31–39.
  • Powell MA, Sill MW, Goodfellow PJ, et al. A phase II trial of brivanib in recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group study. Gynecologic. Elsevier; 2014. Available from: http://www.sciencedirect.com/science/article/pii/S0090825814011585
  • Swift JG, Mukherjee TM, Rowland R. Intercellular junctions in hepatocellular carcinoma. J Submicrosc Cytol. 1983;15:799–810.
  • Mitic LL, Anderson JM. Molecular architecture of tight junctions. Annu Rev Physiol. 1998;60:121–142.
  • Hewitt KJ, Agarwal R, Morin PJ. The claudin gene family: expression in normal and neoplastic tissues. BMC Cancer. 2006;6:186.
  • Morita K, Furuse M, Fujimoto K, et al. Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proc Natl Acad Sci U S A. 1999;96:511–516.
  • English DP, Santin AD. Claudins overexpression in ovarian cancer: potential targets for clostridium perfringens enterotoxin (CPE) based diagnosis and therapy. Int J Mol Sci. 2013;14:10412–10437.
  • Kumar S, Nag A, Mandal CC. A comprehensive review on miR-200c, a promising cancer biomarker with therapeutic potential. Curr Drug Targets. 2015. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25808651
  • Umene K, Yanokura M, Banno K, et al. Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer. Int J Oncol. 2015;46:1498–1506.
  • Morelli M, Scumaci D, Di Cello A, et al. DJ-1 in endometrial cancer: a possible biomarker to improve differential diagnosis between subtypes. Int J Gynecol Cancer. 2014;24:649–658.
  • Cao J, Lou S, Ying M, et al. DJ-1 as a human oncogene and potential therapeutic target. Biochem Pharmacol. 2015;93:241–250.
  • Traver S, Assou S, Scalici E, et al. Cell-free nucleic acids as non-invasive biomarkers of gynecological cancers, ovarian, endometrial and obstetric disorders and fetal aneuploidy. Hum Reprod Update. ESHRE; 2014;20:905–923.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.