UCH-L1 expression and cancer therapy

• US 20050272068A1
• Filed: 03/18/2005
• Published: 12/08/2005
• Est. Priority Date: 03/18/2004
• Status: Abandoned Application

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Liu, Yichin, Lansbury, Peter T.
• Application Number:
  US11/084,716
• Publication Number:
  US 20050272068A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C12Q 1/34 involving hydrolase
• CPC Class Codes: C12Q 1/48 involving transferase
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

Methods are provided of treating cancer with one or more farnesyl transferase inhibitors. Methods are provided for identifying cancers that are particularly susceptible to treatment with one or more farneseyl transferase inhibitors by identifying cancers that express low levels of UCH-L1.

Claims

1. A screening method to identify cancers responsive to farnesyl transferase inhibitors, the method comprising the steps of:

detecting an amount of UCH-L1 in a cancer in a biological sample; and

,

identifying the cancer as;

(i) a farnesyl transferase responsive cancer if the amount of UCH-L1 is below a threshold amount;

or

(ii) a farnesyl transferase non-responsive cancer if the amount of UCH-L1 is above the threshold amount.

2. The method of claim 1, wherein the threshold amount of UCH-L1 is selected from the group consisting of an amount in a reference cell line, an amount in a reference cancer, and an amount that is twice that of normal tissue.

3. The method of claim 1, wherein the amount of UCH-L1 is detected using an assay selected from the group consisting of:

an RNA expression assay, a protein expression assay, an ELISA, and a UCH-L1 activity assay.

4. The method of claim 1, wherein the biological sample is selected from the group consisting of:

tissue biopsy, cell culture, and bodily fluids.

5. A method of treating cancer, the method comprising the steps of

identifying a cancer with a UCH-L1 amount below a threshold amount;

and,

treating a subject having said cancer with a therapeutically effective amount of a farnesyl transferase inhibitor.

6. The method of claim 5, wherein the subject is a human.

7. The method of claim 5, wherein the farnesyl transferase inhibitor is selected from the group consisting of:

SCH66336, L778123, BMS-214662, R115777 and FTI-277.

8. The method of claim 5, wherein two or more different farnesyl transferase inhibitors are administered and wherein said farnesyl transferase inhibitors are independently selected from the group consisting of:

SCH66336, L778123, BMS-214662, R115777 and FTI-277.

9. The method of claim 5, wherein the farnesyl transferase inhibitor is administered in combination with another anticancer drug.

10. A screening method to identify cancers responsive to farnesyl transferase inhibitors, the method comprising the steps of:

detecting an amount of UCH-L1 in a cancer in a patient in vivo; and

,

identifying the cancer as;

(i) a farnesyl transferase responsive cancer if the amount of UCH-L1 is below a threshold amount;

or

(ii) a farnesyl transferase non-responsive cancer if the amount of UCH-L1 is above the threshold amount.

11-16. -16. (canceled)