Methods for determining drug efficacy using cereblon-associated proteins
Use of cereblon-associated proteins as biomarkers for clinical sensitivity to cancer, inflammatory diseases, and patient response to drug treatment.
1. A method of assessing the efficacy of a compound in treating a disease or disorder, comprising:
(a) administering a compound to a subject having a disease or disorder;
(b) obtaining a first cell sample from the subject after administering the compound;
(c) determining the level of IKZF1 and/or IKZF3 in the first cell sample by measuring the protein level of IKZF1 and/or IKZF3; and
(d) comparing the level of IKZF1 and/or IKZF3 from step (c) to the level of the same protein obtained from a reference cell sample,
wherein a decrease in the level of IKZF1 and/or IKZF3 as compared to the reference is indicative of the efficacy of the compound in treating the disease or disorder;
wherein the disease or disorder is a blood cancer; and
wherein the compound is thalidomide, lenalidomide, pomalidomide, 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione or 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt-thereof.
2. The method of claim 1 , wherein the first cell sample is obtained from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast.
3. The method of claim 1 , wherein the reference is prepared by using a second cell sample obtained from the subject prior to administration of the compound to the subject; and wherein the second cell sample is from the same source as the first cell sample.
4. The method of claim 1 , wherein the reference is prepared by using a second cell sample obtained from a healthy subject not having the disease or disorder; and wherein the second cell sample is from the same source as the first cell sample.
5. The method of claim 1 , wherein the blood cancer is multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin's Lymphoma, or mantle cell lymphoma.
6. The method of claim 5 , wherein the blood cancer is multiple myeloma.
7. The method of claim 5 , wherein the blood cancer is chronic lymphocytic leukemia.
8. The method of claim 5 , wherein the blood cancer is non-Hodgkin's Lymphoma.
9. The method of claim 5 , wherein the blood cancer is mantle cell lymphoma.
10. A method of assessing the efficacy of a compound in treating a disease or disorder, comprising:
(a) administering a compound to a subject having a disease or disorder;
(b) obtaining a first cell sample from the subject after administering the compound;
(c) determining the level of IKZF1 and/or IKZF3 in the first cell sample by measuring the protein level of IKZF1 and/or IKZF3; and
(d) comparing the level of IKZF1 and/or IKZF3 from step (c) to the level of the same protein obtained from a reference cell sample,
wherein a decrease in the level of IKZF1 and/or IKZF3 as compared to the reference is indicative of the efficacy of the compound in treating the disease or disorder;
wherein the disease or disorder is an inflammatory disease selected from the group consisting of: systemic lupus erythematosus, Sjogren syndrome and systemic sclerosis; and
wherein the compound is thalidomide, lenalidomide, pomalidomide, 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione or 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable salt-thereof.
11. The method of claim 10 , wherein the reference is prepared by using a second cell sample obtained from the subject prior to administration of the compound to the subject; and wherein the second cell sample is from the same source as the first cell sample.
12. The method of claim 10 , wherein the reference is prepared by using a second cell sample obtained from a healthy subject not having the disease or disorder; and wherein the second cell sample is from the same source as the first cell sample.
13. The method of claim 10 , wherein the disease or disorder is systemic lupus erythematosus.
14. The method of claim 10 , wherein the disease or disorder is Sjogren syndrome.
15. The method of claim 10 , wherein the disease or disorder is systemic sclerosis.