COMPOSITIONS AND METHODS FOR THE TREATMENT OF VprBP-RELATED CANCERS
AssigneeUniversity of Southern California
InventorsWoojin An, Nouri Neamati, Kyunghwan Kim
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Abstract
This disclosure provides methods and compositions to inhibit or suppress tumor growth or to treat cancer by inhibiting VprBP kinase activity. Also provided are methods of determining the effectiveness of the methods and compositions to inhibit or suppress tumor growth or to treat cancer by inhibiting VprBP kinase activity, methods for detecting a cancer, and methods for screening potential agents that inhibit VprBP kinase activity.
Claims22
A method for one or more of:
- a. inhibiting the growth of a cancer cell;
- b. activating tumor suppressor function in a cell comprising functional tumor suppressor genes;
- and
- c. inhibiting H2AT120P in a cell comprising functional H2AT120P, comprising contacting the cell with an effective amount of an agent that inhibits VprBP kinase activity in the cell.
A method for inhibiting the growth of a cancer cell in a patient or treating cancer in a patient, comprising administering to the patient in need thereof an effective amount of one or more of:
- VprBR kinase-specific RNAi, a small molecule inhibitor of VprBP or a polypeptide comprising the amino acid sequence (QTARKSTGGKAPRKQLATKAARK) (SEQ ID NO:
- 12).
A method of determining whether a patient is more likely or less likely to be diagnosed with a VprBR-related cancer, comprising screening a sample isolated from the patient for the presence of VprBP in a sample of the patient, wherein the presence of VprBP is an indication that the patient is more likely to be diagnosed with a VprBR-related cancer in the patient and an absence of VprBR is an indication that the patient is less likely to be diagnosed with a VprBR-related cancer.
A method for determining the effectiveness of treating a VprBR-related cancer in a patient by VprBP inhibition, comprising comparing the expression level of one or more gene selected from Table 2 and Table 3 in a sample isolated of the patient before treatment by administration of a VprBP inhibiting agent with the expression level of the one or more gene in a sample of the patient after treatment, wherein an increased expression of a gene selected from Table 2 or decreased expression of a gene selected from Table 3 is indicative of positive effectiveness of VprBP inhibition in treating the cancer in the patient.
A composition comprising a carrier and a compound of the formula:
- or a pharmaceutically acceptable salt or a solvate thereof, or an equivalent of each thereof.
A composition comprising a carrier and a VprBR kinase-specific RNAi.
An isolated reference polypeptide having a sequence selected from the group of:
- a.
- (SEQ ID NO:
- 4)
- Q-PLRTYSTGLLGGAMENQDI;
- b.
- (SEQ ID NO:
- 5)
- EVALRQENKRPSPRKLS;
- c.
- (SEQ ID NO:
- 6)
- DPDRMFVELSNSSWSEMSPWVIGTNYTLYPMTPAIEQRL;
- d.
- (SEQ ID NO:
- 7)
- YIDLKQTNDVL;
- e.
- (SEQ ID NO:
- 8)
- FATEFV;
- f.
- (SEQ ID NO:
- 9)
- KLLEIPRPS;
- g.
- (SEQ ID NO:
- 10)
- QDAMERV[[Q]]CM;
- or
- h.
- (SEQ ID NO:
- 12)
- QTARKSTGGKAPRKQLATKAARK;
- i. a polypeptide comprising at least two of a. through h.;
- or
- j. or an equivalent thereof, wherein an equivalent thereof comprises a polypeptide that has at least 80% sequence identity to the reference polypeptide, or a polypeptide encoded by a polynucleotide that hybridizes under conditions of high stringency to a polynucleotide or its complement that encodes the reference polypeptide, wherein conditions of high stringency comprise hybridization reaction at about 60° C. in about 1×SSC.
A screen to identify a potential therapeutic agent of inhibiting tumor growth or for tumor suppression, comprising contacting a candidate agent with VprBP, initiating a kinase reaction, wherein the agent is a potential therapeutic agent if a reduction of kinase activity as compared to the kinase activity of VprBP in the absence of the agent is observed.
Dependencies are inferred from the claim text.