METHOD AND COMPOSITION FOR DIAGNOSIS OR TREATMENT OF AGGRESSIVE PROSTATE CANCER
원문보기
IPC분류정보
국가/구분
United States(US) Patent
공개
국제특허분류(IPC7판)
C12N-015/113
G06F-019/22
G06F-019/18
출원번호
US-0119608
(2015-02-19)
공개번호
US-0051281
(2017-02-23)
국제출원번호
PCT/US15/16653
(2015-02-19)
발명자
/ 주소
ABATE-SHEN, Corinne
CALIFANO, Andrea
SHEN, Michael
출원인 / 주소
ABATE-SHEN, Corinne
인용정보
피인용 횟수 :
0인용 특허 :
0
초록▼
Methods, pharmaceutical formulations and medicaments for treating prostate cancer or preventing the progression of a nonaggressive form of prostate cancer to an aggressive form, in a mammal, include a therapeutically effective amount of one or more active agents that reduce the expression or biologi
Methods, pharmaceutical formulations and medicaments for treating prostate cancer or preventing the progression of a nonaggressive form of prostate cancer to an aggressive form, in a mammal, include a therapeutically effective amount of one or more active agents that reduce the expression or biological activity of both Forkhead box protein M1 (FOXM1) and Centromere protein F (CENPF) or biologically active fragments thereof or biologically active fragments thereof selected from the group consisting of an isolated shRNA, siRNA, antisense RNA, antisense DNA, Chimeric Antisense DNA/RNA, microRNA, and ribozymes that are sufficiently complementary to either a gene or an mRNA encoding either FOXM1 or CENPF proteins. A method is also presented for discovering synergistic master regulators of other phenotype transitions, wherein the master regulators are conserved among different species.
대표청구항▼
1. A method for treating prostate cancer or preventing the progression of a nonaggressive form of prostate cancer to an aggressive form, in a mammal, comprising administering to the mammal a therapeutically effective amount of one or more active agents that reduce the expression or biological activi
1. A method for treating prostate cancer or preventing the progression of a nonaggressive form of prostate cancer to an aggressive form, in a mammal, comprising administering to the mammal a therapeutically effective amount of one or more active agents that reduce the expression or biological activity of both Forkhead box protein M1 (FOXM1) (SEQ ID NO: 50) and Centromere protein F (CENPF) (SEQ ID NO: 54) or biologically active fragments thereof or biologically active fragments thereof selected from the group consisting of an isolated shRNA, siRNA, antisense RNA, antisense DNA, Chimeric Antisense DNA/RNA, microRNA, and ribozymes that are sufficiently complementary to either a gene or an mRNA encoding either FOXM1 or CENPF proteins. 2. The method of claim 1, wherein the prostate cancer is aggressive prostate cancer. 3. The method of claim 1, wherein the active agent is administered orally. 4. The method of claim 1, wherein the active agent is administered locally to a prostate gland or prostate tumor. 5. The method of claim 1, wherein the active agent is selected from the group consisting of FOXM1 shRNA#1 SEQ ID NO: 1, FOXM1 shRNA#2 SEQ ID NO: 2; CENPFshRNA#1 SEQ ID NO: 3; CENPFshRNA#2 SEQ ID NO: 4. 6. A pharmaceutical formulation for treating prostate cancer or reducing or preventing the progression of a nonaggressive form of prostate cancer to an aggressive form, comprising a therapeutically effective amount of one or more active agents that reduce the expression or biological activity of both Forkhead box protein M1 (FOXM1) (SEQ ID NO: 50) and Centromere protein F: (CENPF) (SEQ ID NO: 54) selected from the group consisting of an isolated shRNA, siRNA, antisense RNA, antisense DNA, Chimeric Antisense DNA/RNA, microRNA, and ribozymes that are sufficiently complementary to either a gene or an mRNA encoding the FOXM1 or CENPF protein. 7. The pharmaceutical composition of claim 5, wherein the therapeutically effective amount is an amount that produces an effect selected from the group consisting of reducing prostate tumor size, reducing prostate tumor growth, reducing or preventing the progression of a nonaggressive form of prostate cancer to an aggressive form, and metastasizing to a tumor in a different tissue. 8. The pharmaceutical formulation of claim 6, wherein the active agent is selected from the group consisting of FOXM1 shRNA#1 SEQ ID NO: 1, FOXM1 shRNA#2 SEQ ID NO: 2; CENPFshRNA#1 SEQ ID NO: 3; CENPFshRNA#2 SEQ ID NO: 4. 9. A medicament treating prostate cancer or reducing or preventing the progression of a nonaggressive form of prostate cancer to an aggressive form, comprising one or more active agents in a therapeutically effective amount that reduce the expression or biological activity of both Forkhead box protein M1 (FOXM1) (SEQ ID NO: 50) and Centromere protein F (CENPF) (SEQ ID NO: 54) or biologically active fragments thereof selected from the group consisting of an isolated shRNA, siRNA, antisense RNA, antisense DNA, Chimeric Antisense DNA/RNA, microRNA, and ribozymes that are sufficiently complementary to either a gene or an mRNA encoding either FOXM1 or CENPF proteins. 10. The medicament of claim 9, wherein the active agent is selected from the group consisting of FOXM1 shRNA#1 SEQ ID NO: 1, FOXM1 shRNA#2 SEQ ID NO: 2; CENPFshRNA#1 SEQ ID NO: 3; CENPFshRNA#2 SEQ ID NO: 4. 11. A method comprising: (a) receiving, automatically on a processor, data that indicates human gene expression profiles for human tissue in a context of interest comprising a plurality of cell phenotypes including at least one gene expression profile representing a first cell phenotype and at least one other gene expression profile representing a second cell phenotype;(b) determining, automatically on a processor based on the human gene expression profiles, data that indicates an interactome of human tissue in the context of interest;(c) determining, automatically on a processor based on the human gene expression profile, data that indicates a human signature that represents a ranking of genes differentially expressed in the second cell phenotype compared to the first cell phenotype;(d) determining, automatically on a processor based on the interactome of human tissue and the human signature, data that indicates human master regulator molecules most likely to have produced the human signature;(e) receiving, automatically on a processor, data that indicates animal model gene expression profiles for animal tissue in the context of interest based on multiple in vivo perturbations of one or more genetically distinct animals including at least one gene expression profile representing the first cell phenotype and at least one other gene expression profile representing the second cell phenotype;(f) determining, automatically on a processor based on the animal model gene expression profile, data that indicates an interactome of animal tissue in the context of interest;(g) determining, automatically on a processor based on the animal model gene expression profile, data that indicates an animal signature that represents a ranking of genes differentially expressed in the second cell phenotype compared to the first cell phenotype;(h) determining, automatically on a processor based on the interactome of animal tissue and the animal signature, data that indicates animal master regulator molecules most likely to have produced the animal signature; and(i) determining, automatically on a processor based on the human master regulator molecule and the animal master regulator molecules, data that indicates conserved master regulator molecules that are most likely to have produced both the human signature and the animal signature.
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