Methods for determining drug efficacy for the treatment of diffuse large b-cell lymphoma, multiple myeloma, and myeloid cancers

Abstract

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound.

What is claimed is: 
     
         1 . A method of determining whether a compound is immunomodulatory, comprising:
 (a) contacting a first cell with the compound;
 wherein optionally the cell is a cancer cell, or 
 wherein optionally the cell is an immune cell; 
   (b) obtaining a first sample from the first cell from step (a);   (c) determining the level of a biomarker in the first sample, and   (d) comparing the level of the biomarker from step (c) to the level of the same protein obtained from a reference sample, wherein a change in the biomarker level as compared to the reference sample is indicative of the efficacy of the compound as an immunomodulatory compound.   
     
     
         2 . The method of  claim 1 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an immunomodulatory compound. 
     
     
         3 . The method of  claim 1 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an immunomodulatory compound. 
     
     
         4 . A method of treating a cancer, comprising the method of  claim 2  or  3 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated as likely to be efficacious as an immunomodulatory compound. 
     
     
         5 . The method of  claim 1 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an immunomodulatory compound. 
     
     
         6 . The method of  claim 1 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an immunomodulatory compound. 
     
     
         7 . A method of treating a cancer, comprising the method of  claim 5  or  6 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated as unlikely to be efficacious as an immunomodulatory compound. 
     
     
         8 . A method of determining whether a compound is effective as an anti-tumor agent, comprising:
 (a) contacting a first cell with the compound;
 wherein optionally the cell is a cancer cell, or 
 wherein optionally the cell is an immune cell; 
   (b) obtaining a first sample from the first cell from step (a),   (c) determining the level of a biomarker in the first sample; and   (d) comparing the level of the biomarker from step (c) to the level of the same protein(s) obtained from a reference sample, wherein a change in the biomarker level as compared to the reference sample is indicative of the efficacy of the compound as an anti-tumor agent.   
     
     
         9 . The method of  claim 8 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an anti-tumor agent. 
     
     
         10 . The method of  claim 8 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an anti-tumor agent. 
     
     
         11 . A method of treating a cancer, comprising the method of  claim 9  or  10 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated as likely to be efficacious as an anti-tumor agent. 
     
     
         12 . The method of  claim 8 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an anti-tumor agent. 
     
     
         13 . The method of  claim 8 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an anti-tumor agent. 
     
     
         14 . A method of treating a cancer, comprising the method of  claim 12  or  13 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated to be as unlikely to be efficacious as an anti-tumor agent. 
     
     
         15 . The method of any one of  claims 1  to  14 , wherein the contacting in step (a) is in vitro. 
     
     
         16 . The method of any one of  claims 1  to  14 , wherein the contacting in step (a) is in vivo. 
     
     
         17 . A method of assessing the efficacy of a compound in treating cancer, comprising:
 (a) administering a compound to a subject having cancer;   (b) obtaining a first sample from the subject;   (c) determining the level of a biomarker in the first sample; and   (d) comparing the level of the biomarker from step (c) to the level of the same protein obtained from a reference sample, wherein a change in the biomarker level as compared to the reference sample is indicative of the efficacy of the compound in treating the cancer.   
     
     
         18 . The method of  claim 17 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious in treating the cancer. 
     
     
         19 . The method of  claim 17 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious in treating the cancer. 
     
     
         20 . A method of treating a cancer, comprising the method of  claim 18  or  19 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated as likely to be efficacious in treating the cancer. 
     
     
         21 . The method of  claim 17 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious in treating the cancer. 
     
     
         22 . The method of  claim 17 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious in treating the cancer. 
     
     
         23 . A method of treating a cancer, comprising the method of  claim 21  or  22 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated as unlikely to be efficacious in treating the cancer. 
     
     
         24 . A method of selecting a group of cancer subjects for the purposes of predicting clinical response, monitoring clinical response, or monitoring patient compliance to dosing by a compound, comprising:
 (a) administering a compound to a subject;   (b) obtaining a first sample from the subject;   (c) determining the level of a biomarker in the first sample; and   (d) diagnosing the subject as being likely to be responsive to the compound if the level of the biomarker in the first sample is different than the level in a reference sample.   
     
     
         25 . The method of  claim 24 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the subject is likely to be responsive to the compound. 
     
     
         26 . The method of  claim 24 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the subject is likely to be responsive to the compound. 
     
     
         27 . A method of treating a cancer, comprising the method of  claim 25  or  26 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the subject is indicated as likely to be to be responsive to the compound. 
     
     
         28 . The method of  claim 24 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the subject is unlikely to be responsive to the compound. 
     
     
         29 . The method of  claim 24 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the subject is unlikely to be responsive to the compound. 
     
     
         30 . A method of treating a cancer, comprising the method of  claim 28  or  29 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the subject is indicated as unlikely to be to be responsive to the compound. 
     
     
         31 . The method of any one of  claims 1  to  30 , wherein the first sample is obtained from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast. 
     
     
         32 . The method of any one of  claims 1  to  31 , wherein the reference sample is prepared by using a second sample not contacted with the compound. 
     
     
         33 . The method of any one of  claims 9  to  32 , wherein the reference sample is prepared by using a second sample obtained from the subject prior to administration of the compound to the subject. 
     
     
         34 . The method of any one of  claims 1  to  32 , wherein the reference is prepared by using a second sample obtained from a healthy subject not having the cancer. 
     
     
         35 . The method of any one of  claims 1  to  34 , wherein the second sample is from the same source as the first sample. 
     
     
         36 . A method of identifying a subject having a cancer who is likely to be responsive to a treatment compound, comprising:
 (a) administering the treatment compound to a subject having the cancer;   (b) obtaining a sample from the subject;   (c) determining the level of a biomarker in the sample from the subject; and   (d) diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a level of the biomarker in a reference sample.   
     
     
         37 . The method of  claim 36 , wherein the subject is diagnosed as likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is higher than a level of the biomarker in a reference sample. 
     
     
         38 . The method of  claim 36 , wherein the subject is diagnosed as likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is lower than a level of the biomarker in a reference sample. 
     
     
         39 . A method of treating a cancer, comprising the method of  claim 37  or  38 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the subject is diagnosed as likely to be responsive to the treatment compound. 
     
     
         40 . The method of  claim 36 , wherein the subject is diagnosed as unlikely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is higher than a level of the biomarker in a reference sample. 
     
     
         41 . The method of  claim 36 , wherein the subject is diagnosed as unlikely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is lower than a level of the biomarker in a reference sample. 
     
     
         42 . A method of treating a cancer, comprising the method of  claim 40  or  41 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the subject is diagnosed as unlikely to be responsive to the treatment compound. 
     
     
         43 . A method of predicting the responsiveness of a subject having or suspected of having a cancer to a treatment compound, comprising:
 (a) administering the treatment compound to the subject;   (b) obtaining a sample from the subject;   (c) determining the level of a biomarker in the sample from the subject; and   (d) predicting or diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample changes as compared to the level of the biomarker obtained from a reference sample.   
     
     
         44 . The method of  claim 43 , wherein the subject is diagnosed as likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is higher than the level of the biomarker in a reference sample. 
     
     
         45 . The method of  claim 43 , wherein the subject is diagnosed as likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is lower than the level of the biomarker in a reference sample. 
     
     
         46 . A method of treating a cancer, comprising the method of  claim 44  or  45 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the subject is diagnosed as likely to be responsive to the treatment compound. 
     
     
         47 . The method of  claim 43 , wherein the subject is diagnosed as unlikely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is higher than the level of the biomarker in a reference sample. 
     
     
         48 . The method of  claim 43 , wherein the subject is diagnosed as unlikely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject is lower than the level of the biomarker in a reference sample. 
     
     
         49 . A method of treating a cancer, comprising the method of  claim 47  or  48 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the subject is diagnosed as unlikely to be responsive to the treatment compound. 
     
     
         50 . A method of monitoring the efficacy of a treatment of a cancer in a subject with a treatment compound, comprising:
 (a) administering the treatment compound to a subject having cancer;   (b) obtaining a sample from the subject;   (c) determining the level of a biomarker in the sample from the subject; and   (d) comparing the level of the biomarker in the sample with the level of the biomarker obtained from a reference sample, wherein a change in the level as compared to the reference sample is indicative of the efficacy of the treatment compound in treating the cancer in the subject.   
     
     
         51 . The method of  claim 50 , wherein an increased level of the biomarker in the sample as compared to the of level of the biomarker in the reference sample is indicative of the efficacy of the treatment compound in treating the cancer in the subject. 
     
     
         52 . The method of  claim 50 , wherein a decreased level of the biomarker in the sample as compared to the of level of the biomarker in the reference sample is indicative of the efficacy of the treatment compound in treating the cancer in the subject. 
     
     
         53 . A method of treating a cancer, comprising the method of  claim 51  or  52 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated to be efficacious in treating the cancer in the subject. 
     
     
         54 . The method of  claim 50 , wherein an increased level of the biomarker in the sample as compared to the of level of the biomarker in the reference sample is indicative of the lack of efficacy of the treatment compound in treating the cancer in the subject. 
     
     
         55 . The method of  claim 50 , wherein a decreased level of the biomarker in the sample as compared to the of level of the biomarker in the reference sample is indicative of the lack of efficacy of the treatment compound in treating the cancer in the subject. 
     
     
         56 . A method of treating a cancer, comprising the method of  claim 54  or  55 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated to have a lack of efficacy in treating the cancer in the subject. 
     
     
         57 . The method of any one of  claims 36  to  56 , wherein the sample is obtained from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast. 
     
     
         58 . The method of any one of  claims 36  to  57 , wherein the reference sample is prepared by using a second sample not contacted with the compound. 
     
     
         59 . The method of any one of  claims 36  to  58 , wherein the reference sample is prepared by using a second sample obtained from the subject prior to administration of the compound to the subject. 
     
     
         60 . The method of any one of  claims 36  to  58 , wherein the reference is prepared by using a second sample obtained from a healthy subject not having the cancer. 
     
     
         61 . The method of any one of  claims 36  to  60 , wherein the second sample is from the same source as the first sample. 
     
     
         62 . The method of any one of  claims 1  to  61 , wherein step (c) comprises:
 (i) contacting the proteins within the sample from step (b) with a first antibody that immunospecifically binds to the biomarker; 
 (ii) contacting the proteins bound to the first antibody with a second antibody with a detectable label, wherein the second antibody immunospecifically binds to the biomarker, and wherein the second antibody immunospecifically binds to a different epitope on the biomarker than the first antibody; 
 (iii) detecting the presence of second antibody bound to the biomarker; and 
 (iv) determining the amount of the biomarker based on the amount of detectable label in the second antibody. 
 
     
     
         63 . The method of any one of  claims 1  to  62 , wherein step (c) comprises using immunohistochemistry to determine the level of the biomarker. 
     
     
         64 . The method of  claim 63 , wherein step (c) comprises:
 (i) contacting proteins within the first sample from step (b) with a first antibody that immunospecifically binds to a biomarker, the first antibody being coupled with a first detectable label;   (ii) contacting the proteins within the first sample from step (b) with a second antibody that immunospecifically binds to a cancer biomarker, the second antibody being coupled with a second detectable label;   (iii) detecting the presence of the first antibody and the second antibody bound to the proteins; and   (iv) determining the level of the biomarker based on the amount of detectable label in the first antibody, and determining the level of the cancer biomarker based on the amount of detectable label in the second antibody.   
     
     
         65 . The method of  claim 64 , wherein the cancer biomarker is CD138. 
     
     
         66 . The method of  claim 64  or  65 , wherein H-score is used to determine the level of the biomarker. 
     
     
         67 . The method of  claim 66 , wherein H-score is used to determine the level of the biomarker when the level of the cancer biomarker is higher than a reference level. 
     
     
         68 . The method of any one of  claims 1  to  62 , wherein step (c) comprises:
 (i) contacting RNA within the first sample with a primer comprising a sequence specifically binding to the RNA to generate a first DNA molecule having a sequence complementary to the RNA; 
 (ii) amplifying the DNA corresponding to a segment of a gene encoding the biomarker; and 
 (iii) determining the RNA level of the biomarker based on the amount of the amplified DNA. 
 
     
     
         69 . A method of predicting patient response to compound treatment in a cancer patient, the method comprising:
 (a) obtaining a sample comprising cells from the patient,   (b) culturing the cells in the presence or absence of the compound,   (c) purifying protein or nucleic acid (e.g., a RNA, such as mRNA, or DNA) from the cultured cells, and   (d) measuring the presence or absence of a biomarker.   
     
     
         70 . The method of  claim 69 , wherein the presence of the biomarker indicates or is predictive of the likelihood of patient response to the compound treatment. 
     
     
         71 . The method of  claim 69 , wherein the absence of the biomarker indicates or is predictive of the likelihood of patient response to the compound treatment. 
     
     
         72 . A method of treating a cancer, comprising the method of  claim 70  or  71 , the method further comprising (e) administering to the subject a therapeutically effective amount of the compound when a patient is predicted to have a response to the compound treatment. 
     
     
         73 . The method of  claim 69 , wherein the presence of the biomarker indicates or is predictive of a decreased likelihood of patient response to the compound treatment. 
     
     
         74 . The method of  claim 69 , wherein the absence of the biomarker indicates or is predictive of a decreased likelihood of patient response to the compound treatment. 
     
     
         75 . A method of treating cancer, comprising the method of  claim 73  or  74 , the method further comprising (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when a patient is not predicted to have a response to the compound treatment. 
     
     
         76 . A method of monitoring tumor response to compound treatment in a cancer patient, the method comprising
 (a) obtaining a first sample from the patient,   (b) measuring the expression of a biomarker in the first sample,   (c) administering a compound to the patient,   (d) thereafter, obtaining a second sample from the patient,   (e) measuring biomarker expression in the second sample, and   (f) comparing the levels of biomarker expression in the first and second samples.   
     
     
         77 . The method of  claim 76 , wherein an increased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective tumor response. 
     
     
         78 . The method of  claim 76 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective tumor response. 
     
     
         79 . A method of treating a tumor, comprising the method of  claim 77  or  78 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of the compound when there is a likelihood of an effective tumor response. 
     
     
         80 . The method of  claim 76 , wherein an increased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective tumor response. 
     
     
         81 . The method of  claim 76 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective tumor response. 
     
     
         82 . A method of treating a tumor, comprising the method of  claim 80  or  81 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of a therapy other than the compound when there is not a likelihood of an effective tumor response. 
     
     
         83 . A method of treating a subject with a compound, the method comprising
 (a) obtaining a first sample from the patient,   (b) measuring the expression of a biomarker in the first sample,   (c) administering a compound to the patient,   (d) thereafter, obtaining a second sample from the patient,   (e) measuring biomarker expression in the second sample,   (f) comparing the levels of biomarker expression in the first and second samples.   
     
     
         84 . The method of  claim 83 , wherein an increased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective tumor response. 
     
     
         85 . The method of  claim 83 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective tumor response. 
     
     
         86 . The method of  claim 84  or  85 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of the compound when there is a likelihood of an effective tumor response. 
     
     
         87 . The method of  claim 83 , wherein an increased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective tumor response. 
     
     
         88 . The method of  claim 83 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective tumor response. 
     
     
         89 . The method of  claim 87  or  88 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of a therapy other than the compound when there is not a likelihood of an effective tumor response. 
     
     
         90 . A method of monitoring interferon (IFN) therapy treatment response to compound treatment in a cancer patient, the method comprising
 (a) obtaining a first sample from the patient,   (b) measuring the expression of a biomarker in the first sample,   (c) administering one or more compounds to the patient,   (d) thereafter, obtaining a second sample from the patient,   (e) measuring biomarker expression in the second sample, and   (f) comparing the levels of biomarker expression in the first and second samples.   
     
     
         91 . The method of  claim 90 , wherein an increased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective IFN therapy treatment response. 
     
     
         92 . The method of  claim 90 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective IFN therapy treatment response. 
     
     
         93 . A method of treating a cancer, comprising the method of  claim 91  or  92 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of the compound when there is a likelihood of an effective IFN therapy treatment response. 
     
     
         94 . The method of  claim 90 , wherein an increased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective IFN therapy treatment response. 
     
     
         95 . The method of  claim 90 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective IFN therapy treatment response. 
     
     
         96 . A method of treating a cancer, comprising the method of  claim 91  or  92 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of a therapy other than the compound when there is not a likelihood of an effective IFN therapy treatment response. 
     
     
         97 . The method of any one of  claims 62  to  89 , wherein the first sample is obtained from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast. 
     
     
         98 . The method of any one of  claims 69  to  90 , wherein the second sample is obtained from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast. 
     
     
         99 . The method of any one of  claims 62  to  91 , wherein the second sample is from the same source as the first sample. 
     
     
         100 . The method of any one of  claims 69  to  99 , wherein the measuring step(s) comprises:
 (i) contacting proteins within the sample with a first antibody that immunospecifically binds to the biomarker; 
 (ii) contacting the proteins bound to the first antibody with a second antibody with a detectable label, wherein the second antibody immunospecifically binds to the biomarker, and wherein the second antibody immunospecifically binds to a different epitope on the biomarker than the first antibody; 
 (iii) detecting the presence of second antibody bound to the biomarker; and 
 (iv) determining the amount of the biomarker based on the amount of detectable label in the second antibody. 
 
     
     
         101 . The method of any one of  claims 62  to  100 , wherein the measuring step(s) comprises using immunohistochemistry to determine the level of the biomarker. 
     
     
         102 . The method of  claim 101 , wherein the measuring step(s) comprises:
 (i) contacting proteins within the sample with a first antibody that immunospecifically binds to a biomarker, the first antibody being coupled with a first detectable label;   (ii) contacting the proteins within the sample with a second antibody that immunospecifically binds to a cancer biomarker, the second antibody being coupled with a second detectable label;   (iii) detecting the presence of the first antibody and the second antibody bound to the biomarker; and   (iv) determining the level of the biomarker based on the amount of detectable label in the first antibody, and determining the level of the cancer biomarker based on the amount of detectable label in the second antibody.   
     
     
         103 . The method of  claim 102 , wherein the cancer biomarker is CD138. 
     
     
         104 . The method of  claim 102  or  103 , wherein H-score is used to determine the level of the biomarker. 
     
     
         105 . The method of  claim 104 , wherein H-score is used to determine the level of the biomarker when the level of the cancer biomarker is higher than a reference level. 
     
     
         106 . The method of any one of  claims 62  to  91 , wherein the measuring step(s) comprises:
 (i) contacting the RNA within the sample with a primer comprising a sequence specifically binding to the RNA to generate a first DNA molecule having a sequence complementary to the RNA; 
 (ii) amplifying the DNA corresponding to a segment of a gene encoding the biomarker; and 
 (iii) determining the RNA level of the biomarker based on the amount of the amplified DNA. 
 
     
     
         107 . The method of anyone of  claims 1  to  106 , wherein the cancer is diffuse large B-cell lymphoma (DLBCL). 
     
     
         108 . The method of anyone of  claims 1  to  106 , wherein the cancer is multiple myeloma (MM). 
     
     
         109 . The method of anyone of  claims 1  to  106 , wherein the cancer is myelodysplastic syndrome (MDS). 
     
     
         110 . The method of  claim 109 , wherein the MDS is a MDS with deletion of chromosome 5q (del(5q)). 
     
     
         111 . The method of anyone of  claims 1  to  106 , wherein the cancer is acute myeloid leukemia (AML). 
     
     
         112 . The method of anyone of  claims 1  to  106 , wherein the cancer is mantle cell lymphoma (MCL). 
     
     
         113 . The method of anyone of  claims 1  to  106 , wherein the cancer is follicular lymphoma (FL). 
     
     
         114 . The method of anyone of  claims 1  to  106 , wherein the cancer is acute myeloblastic leukemia (AML). 
     
     
         115 . The method of anyone of  claims 1  to  106 , wherein the cancer is chronic lymphocytic leukemia (CLL). 
     
     
         116 . The method of anyone of  claims 1  to  106 , wherein the cancer is non-Hodgkin's lymphoma (NHL). 
     
     
         117 . The method of anyone of  claims 1  to  106 , wherein the cancer is hairy cell leukemia. 
     
     
         118 . The method of anyone of  claims 1  to  106 , wherein the cancer is chronic myelogenous leukemia (CML). 
     
     
         119 . The method of anyone of  claims 1  to  106 , wherein the cancer is AIDS-related Kaposi sarcoma. 
     
     
         120 . The method of anyone of  claims 1  to  106 , wherein the cancer is a malignant melanoma. 
     
     
         121 . A method of monitoring IFN therapy treatment response to compound treatment in a patient having an IFN-associated disorder, the method comprising
 (a) obtaining a first sample from the patient,   (b) measuring the expression of a biomarker in the first sample,   (c) administering one or more compounds to the patient,   (d) thereafter, obtaining a second sample from the patient,   (e) measuring biomarker expression in the second sample, and   (f) comparing the levels of biomarker expression in the first and second samples.   
     
     
         122 . The method of  claim 121 , wherein an increased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective IFN therapy treatment response. 
     
     
         123 . The method of  claim 121 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates the likelihood of an effective IFN therapy treatment response. 
     
     
         124 . A method of treating an IFN-associated disorder, comprising the method of  claim 122  or  123 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of the compound when there is a likelihood of an effective IFN therapy treatment response. 
     
     
         125 . The method of  claim 121 , wherein an increased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective IFN therapy treatment response. 
     
     
         126 . The method of  claim 121 , wherein a decreased level of biomarker expression in the second sample after compound administration indicates a decreased likelihood of an effective IFN therapy treatment response. 
     
     
         127 . A method of treating an IFN-associated disorder, comprising the method of  claim 125  or  126 , wherein the method further comprises (g) administering to the subject a therapeutically effective amount of a therapy other than the compound when there is not a likelihood of an effective IFN therapy treatment response. 
     
     
         128 . The method of any one of  claims 106  to  112 , wherein the first sample is obtained from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast. 
     
     
         129 . The method of any one of  claims 106  to  113 , wherein the second sample is obtained from a tumor biopsy, node biopsy, or a biopsy from bone marrow, spleen, liver, brain or breast. 
     
     
         130 . The method of any one of  claims 106  to  114 , wherein the second sample is from the same source as the first sample. 
     
     
         131 . The method of any one of  claims 120  to  129 , wherein the measuring step(s) comprises:
 (i) contacting proteins within the sample with a first antibody that immunospecifically binds to the biomarker; 
 (ii) contacting the proteins bound to the first antibody with a second antibody with a detectable label, wherein the second antibody immunospecifically binds to the biomarker, and wherein the second antibody immunospecifically binds to a different epitope on the biomarker than the first antibody; 
 (iii) detecting the presence of second antibody bound to the biomarker; and 
 (iv) determining the amount of the biomarker based on the amount of detectable label in the second antibody. 
 
     
     
         132 . The method of any one of  claims 120  to  130 , wherein the measuring step(s) comprises using immunohistochemistry to determine the level of the biomarker. 
     
     
         133 . The method of any one of  claims 120  to  130 , wherein the measuring step(s) comprises:
 (i) contacting the RNA within the sample with a primer comprising a sequence specifically binding to the RNA to generate a first DNA molecule having a sequence complementary to the RNA; 
 (ii) amplifying the DNA corresponding to a segment of a gene encoding the biomarker; and 
 (iii) determining the RNA level of the biomarker based on the amount of the amplified DNA. 
 
     
     
         134 . The method of anyone of  claims 121  to  133 , wherein the IFN-associated disorder is conyloma accuminata. 
     
     
         135 . The method of anyone of  claims 121  to  133 , wherein the IFN-associated disorder is chronic hepatitis B. 
     
     
         136 . The method of anyone of  claims 121  to  133 , wherein the IFN-associated disorder is chronic hepatitis C. 
     
     
         137 . The method of anyone of  claims 121  to  133 , wherein the IFN-associated disorder is relapsing-remitting multiple sclerosis. 
     
     
         138 . The method of anyone of  claims 121  to  133 , wherein the IFN-associated disorder is chronic granulomatous disease. 
     
     
         139 . The method of any one of  claims 1  to  138 , wherein the level of the biomarker is measured by determining the mRNA level of the biomarker. 
     
     
         140 . The method of any one of  claims 1  to  138 , wherein the level of the biomarker is measured by determining the cDNA level of the biomarker. 
     
     
         141 . The method of any one of  claims 1  to  138 , wherein the level of the biomarker is measured by determining the protein level of the biomarker. 
     
     
         142 . The method of anyone of  claims 1  to  141 , wherein the biomarker is a cereblon (CRBN)-associated protein (CAP). 
     
     
         143 . The method of  claim 142 , wherein the CAP is ABCE1, ACLY, ACTB, ALDOA, ARID1A, C7ORF42, COPS6, CPSF6, CSNK1A1, CSNK2A1, CTPS, CRBN, DDB1, DDIT4, DDX17, DDX21, DDX58, DDX58, DDX60, DDX60L, DHX9, DNAJC1, DUT, EEF1A1, EEF1AL3, EEF1G, EIF2S1, EIF2S2, EIF3J, EIF4A1, EWSR1, FASN, FBXO21, FERMT3, FUBP1, G3BP1, G3BP2, GBE1, GBP1, GNAS, GNB2L1, GNB3, H2AFJ, H2AFX, H2AFZ, HIST1H1A, HIST1H1B, HIST1H1C, HIST1H1D, HIST1H1E, HIST1H2AA, HNRNPA2B1, HNRNPC, HNRNPH2, HNRNPR, HSPA1A, HSPA1B, HSPA8, HSPA9, IFI16, IFI27, IFI27L2, IFI35, IFI44, IFI44L, IFI6, IFIH1, IFIT1, IFIT2, IFIT3, IFIT5, IFITM2, IFITM3, IFN, IFNA16, IFNA5, IFNG, IFNGR1, IGF2BP2, IKZF1 (Ikaros), IKZF3 (Aiolos), ILF3, IPO5, IRF1, IRF2, IRF3, IRF4, IRF7, IRF8, IRF9, ISG15, ISG20, KCNAB2, MACF1, MCM2, MCM7, MX1, MX2, MYH10, NACA, NAP1L2, NCL, NEDD8, NUP88, OAS1, OAS2, OAS3, OASL, PABPC1, PABPC4, PCM1, PDXK, PPAT, PRKDC, PTPRC, PTRH2, RPL10A, RPL11, RPL12, RPL13A, RPL14, RPL15, RPL18A, RPL19, RPL21, RPL3, RPL30, RPL4, RPL7, RPL7A, RPL9, RPLP1, RPLP2, RPS13, RPS16, RPS19, RPS2, RPS6, SEC23B, SEC24A, SEC24C, SMC4, SND1, a STAT, a STAT-PO 4 , STAT3, SYNCRIP, TBK1, TBK1-PO 4 , TBL1XR1, TLR1, TLR3, TLR4, TLR7, TLR8, TPD52, TUBA1A, TUBA1B, TUBA1C, UAP1, UBA52, UBAP2L, UBB, UBE2O, UBE2Q1, USP15, VAPA, XAF1, XRCC6, YWHAE, ZFP91, or any combination thereof. 
     
     
         144 . The method of  claim 142  or  143 , wherein the CAP is an IFN pathway protein. 
     
     
         145 . The method of  claim 144 , wherein the IFN pathway protein is an IFN Regulatory Factor (IRF), 
     
     
         146 . The method of  claim 145 , wherein the IRF is selected from a group consisting of IRF1, IRF3, IRF4, IRF7, and IRF9, or any combination thereof. 
     
     
         147 . The method of any one of  claims 144  to  146 , wherein the IFN pathway protein is DDX58, IFI27, IFIH1, IFIT1, IFIT3, IFITM3, IFN, ISG15, OAS3, a STAT, a STAT-PO 4 , TBK1, TBK1-PO 4 , XAF1, or any combination thereof. 
     
     
         148 . The method of any one of  claims 144  to  147 , wherein the IFN pathway protein is DDX58, DDX60, DDX60L, GBP1, IFI16, IFI27, IFI27L2, IFI35, IFI44, IFI44L, IFI6, IFIH1, IFIT1, IFIT2, IFIT3, IFIT5, IFITM2, IFNA16, IFNA5, IFNG, IFNGR1, IRF1, IRF2, IRF4, IRF7, IRF8, ISG15, ISG20, MX1, MX2, OAS1, OAS2, OAS3, OASL, TLR1, TLR3, TLR4, TLR7, TLR8, or any combination thereof. 
     
     
         149 . The method of any one of  claims 142  to  148 , wherein the CAP is IKZF1 (Ikaros). 
     
     
         150 . The method of any one of  claims 142  to  149 , wherein the CAP IKZF3 (Aiolos). 
     
     
         151 . The method of any one of  claims 142  to  150 , wherein the CAP is Ikaros and Aiolos. 
     
     
         152 . The method of any one of  claims 142  to  151 , wherein the CAP is CRBN. 
     
     
         153 . The method of any one of  claims 142  to  152 , wherein the CAP is CSNK1A1. 
     
     
         154 . The method of  claim 153 , wherein the CAP is CSNK1A1 and IFN. 
     
     
         155 . The method of any one of  claims 142  to  154 , wherein the CAP is ZFP91. 
     
     
         156 . The method of any one of  claims 1  to  155 , wherein the compound is a cereblon-binding compound. 
     
     
         157 . The method of  claim 156 , wherein the compound is lenalidomide, pomalidomide, thalidomide, 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione (Compound A), or 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione (Compound B). 
     
     
         158 . The method of  claim 157 , wherein the compound is lenalidomide. 
     
     
         159 . The method of  claim 158 , wherein the compound is a stereoisomer of lenalidomide, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph of lenalidomide. 
     
     
         160 . The method of  claim 157 , wherein the compound is pomalidomide. 
     
     
         161 . The method of  claim 160 , wherein the compound is a stereoisomer of pomalidomide, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph of pomalidomide. 
     
     
         162 . The method of  claim 157 , wherein the compound is thalidomide. 
     
     
         163 . The method of  claim 162 , wherein the compound is a stereoisomer of thalidomide, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph of thalidomide. 
     
     
         164 . The method of  claim 157 , wherein the compound is Compound A. 
     
     
         165 . The method of  claim 164 , wherein the compound is a stereoisomer of Compound A, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph of Compound A. 
     
     
         166 . The method of  claim 157 , wherein the compound is Compound B. 
     
     
         167 . The method of  claim 166 , wherein the compound is a stereoisomer of Compound B, or a pharmaceutically acceptable salt, solvate, hydrate, co-crystal, clathrate, or polymorph of Compound B.