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(12) Patent Application Publication (10) Pub. No.: US 2013/0274315 A1 Birrer Et Al US 201302743 15A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0274315 A1 Birrer et al. (43) Pub. Date: Oct. 17, 2013 (54) PRO-ANGIOGENC GENES IN OVARAN (60) Provisional application No. 60/901,455, filed on Feb. TUMORENDOTHELIAL CELL, SOLATES 14, 2007. (71) Applicants: The University of Texas MD Anderson Publication Classification Cancer Center, Houston, TX (US); The Government of the U.S.A as (51) Int. Cl. represented by the Secretary of the CI2O I/68 (2006.01) Department of He, Rockville, MD (US) (52) U.S. Cl. CPC .................................... CI2O I/6886 (2013.01) (72) Inventors: Michael J. Birrer, Mt. Airy, MD (US); USPC ............... 514/44A: 435/6.12: 506/9: 435/7.1 Tomas A. Bonome, Washington, DC (US); Anil Sood, Pearland, TX (US); (57) ABSTRACT Chunhua Lu, Missouri City, TX (US) A gene profiling signature for ovarian tumor endothelial cells is disclosed herein. The gene signature can be used to diag nosis or prognosis an ovarian tumor, identify agents to treat an (21) Appl. No.: 13/863,219 ovariantumor, to predict the metastatic potential of an ovarian tumor and to determine the effectiveness of ovarian tumor (22) Filed: Apr. 15, 2013 treatments. Thus, methods are provided for identifying agents that can be used to treat ovarian cancer, for determining the effectiveness of an ovarian tumor treatment, or to diagnose or Related U.S. Application Data prognose an ovarian tumor. Methods of treatment are also (60) Division of application No. 12/541,729, filed on Aug. disclosed which include administering a composition that 14, 2009, now Pat. No. 8,440,393, which is a continu includes a specific binding agent that specifically binds to one ation-in-part of application No. PCT/US2008/054014, of the disclosed ovarian endothelial cell tumor-associated filed on Feb. 14, 2008. molecules and inhibits ovarian tumor in the Subject. Patent Application Publication Oct. 17, 2013 Sheet 1 of 20 US 2013/02743 15 A1 XNE in re E. as a as ecs : , , , N iii. s: d. c. X : 3. y; C3 g f ESO S 9. 9. EY. 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HeyA8 MOEC EY-2 Acti EY-2 Acti Patent Application Publication Oct. 17, 2013 Sheet 18 of 20 US 2013/02743 15 A1 w : 4. res w s: ^ Patent Application Publication Oct. 17, 2013 Sheet 19 of 20 US 2013/02743 15 A1 FG. 6 Corio E22 is EX-2 in E2H2 is as SRNAC- sissiC Si3NAi Si3NA FEW No. of positive by wasses C33 estin Pericyte coverage (%) erge 31 & essi s 4. S 3 Patent Application Publication Oct. 17, 2013 Sheet 20 of 20 US 2013/02743 15 A1 & w sias WNo. 8Associo 'oh, : US 2013/02743 15 A1 Oct. 17, 2013 PRO-ANGOGENC GENES IN OVARAN develop chemoresistance and die as a result of their cancer. TUMORENDOTHELIAL CELL, SOLATES Thus, a need exists to identify alternative treatments for ova rian cancer. CROSS REFERENCE TO RELATED APPLICATIONS SUMMARY OF THE DISCLOSURE 0001. This is a divisional of U.S. patent application Ser. 0008. A gene profiling signature is disclosed herein that No. 12/541,729, filed Aug. 14, 2009, which is a continuation can be used to predict clinical outcome and develop therapeu in-part application of International Patent Application PCT/ tics for treating ovarian cancer in a subject. For example, the US2008/054014, filed Feb. 14, 2008, designating the United ovarian endothelial cell tumor-associated molecules identi States and published in English as WO 2008/101118, which fied by the gene profile signature can serve as prognostic claims the benefit of U.S. Provisional Application No. indicators as well as targets for specific therapeutic molecules 60/901,455, filed on Feb. 14, 2007. The entire contents of that can reduce or eliminate ovarian cancer. Thus, methods of these prior applications are incorporated herein by reference. identifying an agent for treating an ovarian tumor are pro vided. In some examples, the methods include contacting a ACKNOWLEDGMENT OF GOVERNMENT cell. Such as an ovarian tumor cell or an ovarian tumor endot SUPPORT helial cell, with one or more test agents under conditions sufficient for the one or more test agents to alter the activity of 0002 This invention was made with government support at least one ovarian endothelial cell tumor-associated mol under contract CA083639 awarded by the National Institutes ecule listed in any of Tables 1-5. The method includes detect of Health. The government has certain rights in the invention. ing the activity of the at least one ovarian endothelial cell tumor-associated molecule in the presence and absence of the FIELD OF THE DISCLOSURE one or more test agents. The activity of the at least one ovarian 0003. This disclosure relates to the field of ovarian cancer endothelial cell tumor-associated molecule in the presence of and in particular, to methods for treating ovarian cancer by the one or more test agents is then compared to the activity in targeting ovarian endothelial cell tumor-associated molecules the absence of such agents to determine if there is differential identified by an ovarian tumor endothelial cell gene expres expression of the at least one ovarian endothelial cell tumor sion profile and methods for identifying therapeutic agents. associated molecule. Differential expression of the ovarian endothelial cell tumor-associated molecule in the presence of BACKGROUND the test agent(s) indicates that the one or more test agents can be used to treat an ovarian tumor. 0004 Ovarian cancer is the fifth most common form of 0009 Methods are also provided for treating an ovarian cancer in women in the United States, accounting for three tumor. In some examples, the method includes administering percent of the total number of cancer cases and twenty-six to the subject a therapeutically effective treatment to inhibit percent of those occurring in the female genital tract. The ovarian tumor growth. In an example, the treatment includes American Cancer Society estimated that 15,310 deaths would administering a therapeutically effective amount of a specific be caused in women living in the United States in 2006. A binding agent that binds with high specificity to one of the large majority of women who die of ovarian cancer will have ovarian endothelial cell tumor-associated molecules listed in had serous carcinoma of the ovarian epithelium, a condition Tables 1, 2, 4 or 5 and alters expression or activity of the which occurs in sixty percent of all cases of ovarian cancer molecules, thereby treating the ovarian tumor in the Subject (Boring et al., Cancer J. Clin. 44: 7-26, 1994). (for example, by decreasing tumor vascular growth, tumor 0005 Women with ovarian cancer are typically asymp growth or tumor volume). In particular examples, the specific tomatic until the cancer has metastasized. As a result, most binding agent preferentially binds to and inhibits expression women with ovarian cancer are not diagnosed until the cancer or activity of one of the ovarian endothelial cell tumor-asso has progressed to an advanced and usually incurable stage ciated molecules that is upregulated in an ovarian tumor (Boente et al., Curr: Probl.
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