Methods of treatment of cancer with reduced UBB expression
The present invention provides compositions comprising a UBC antagonist and methods of use thereof for treating cancer in a patient. In some embodiments, the cancer patient may have a reduced expression level of a UBB gene product. Further provided are reagents and methods for detection of a UBB and/or UBC gene product.
1. A method of treating a patient having cancer, comprising
identifying a patient having cancer with (i) a reduced expression level of a ubiquitin B (UBB) gene product or (ii) a ratio of an expression level of a ubiquitin C (UBC) gene product to an expression level of a ubiquitin B (UBB) gene product that is greater than 1.25, and
administering to the patient a therapeutically effective amount of a ubiquitin C (UBC) antagonist.
2. The method of claim 1 , wherein the cancer is selected from the group consisting of uterine sarcoma, endometrial carcinoma, and ovarian adenocarcinoma.
3. The method of claim 1 , wherein the cancer is ovarian adenocarcinoma.
4. The method of claim 1 , comprising measuring the copy number of the UBB gene in a sample of the patient.
5. The method of claim 1 , comprising measuring the expression level of the UBB gene product or the expression level of the UBC gene product in a sample of the patient.
6. The method of claim 1 , comprising administering to the patient a chemotherapeutic drug.
7. The method of claim 6 , wherein the chemotherapeutic drug is cisplatin.
8. The method of claim 6 , wherein the chemotherapeutic drug causes a DNA damage response (DDR) in the patient.
9. The method of claim 1 , wherein the UBC antagonist is an anti-sense nucleic acid, a short hairpin RNA (shRNA) or a short inhibitory RNA (siRNA).
10. The method of claim 9 , wherein the shRNA targets the nucleic acid sequence set forth in SEQ ID NO: 1.
11. The method of claim 1 , wherein the UBC antagonist is a compound.
12. The method of claim 11 , wherein the UBC antagonist is a small molecule compound.