US 2003/0224422 A1 · Pre-and post therapy gene expression profiling to identify drug targets

A method for identifying genes and their expression products as screening targets for drugs which may be used to improve treatment of a selected condition, the method comprising:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the selected therapy;
(b) determining the expression level of said one or more genes in a second sample from said patient following said treatment with the selected therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b);
wherein a gene whose expression level is significantly increased or significantly decreased following treatment with the selected therapy is identified, along with its expression products, as a screening target for drugs which may be used to improve treatment of the selected condition with the selected therapy.

1 more element

A method for identifying genes and their expression products as screening targets for inhibitors which may be used to improve treatment of a selected condition with a selected therapy comprising:

(a) determining the expression level of one or more genes in a first sample from a patient affected by from the selected condition prior to treatment with the selected therapy;
(b) determining the expression level of said one or more genes in a second sample from said patient following said treatment with the selected therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to identify genes whose expression level is significantly increased following treatment with the selected therapy;
(d) repeating steps (a), (b), and (c) for each patient in a population of patients affected by the selected condition;
(e) determining which patients responded favorably to the selected therapy and which patients did not respond favorably to the selected therapy;
and
(f) comparing the genes whose expression level is significantly;
increased following treatment with the selected therapy in patients who responded favorably to the selected therapy with the genes whose expression level is significantly increased following treatment with the selected therapy in patients who did not respond favorably to the selected therapy, to thereby identify genes for which a significant increase in expression level following treatment with the selected therapy is correlated with a failure to respond favorably to the selected therapy;
wherein a gene whose increase inexpression level is correlated with a failure to respond favorably to the selected therapy is identified, along with its expression products, as a screening target for inhibitors which may be used to improve treatment of said selected condition with said selected therapy.

6 more elements

A method for identifying genes and their expression products as screening targets for inhibitors which may be used to treat a selected condition, said method comprising:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with a selected therapy;
(b) determining the expression level of said one or more genes in a second sample from said patient following said treatment with the selected therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to identify genes whose expression level is significantly increased following treatment with the selected therapy;
(d) repeating steps (a)-(c) for each patient in a population of patients affected by the selected condition;
(e) determining which patients responded favorably to the selected therapy and which patients did not respond favorably to the selected therapy;
and
(f) comparing the genes whose expression level is significantly increased following treatment with the selected therapy in patients who responded favorably to the selected therapy with the genes whose expression level increased following treatment with the selected therapy in patients who did not respond favorably to the selected therapy, to thereby identify genes for which a significant increase in expression level following treatment with the selected therapy is correlated with a failure to respond favorably to the selected therapy;
wherein a gene whose increase in expression level is correlated with a failure to respond favorably to the selected therapy is identified, along with its expression products, as a screening target for inhibitors which may be used to treat the selected condition.

5 more elements

A method for identifying genes and their expression products as screening targets for mimics or activators which may be used to improve treatment of a selected condition with a selected therapy comprising:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the selected therapy;
(b) determining the expression level of said one or more genes in a second sample from said patient following said treatment with the selected therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to identify genes whose expression level is significantly decreased following treatment with the selected therapy;
(d) repeating steps (a)-(c) for each patient in a population of patients affected by the selected condition;
and
(e) determining which patients responded favorably to the selected therapy and which patients did not respond favorably to the selected therapy;
and
(f) comparing the genes whose expression level is significantly decreased following treatment with the selected therapy in patients who responded favorably to the selected therapy with the genes whose expression level is significantly decreased following treatment with the selected therapy in patients who did not respond favorably to the selected therapy, to thereby identify genes for which a decrease in expression level following treatment with the selected therapy is correlated with a failure to respond favorably to the selected therapy;
wherein a gene whose decrease in expression level is correlated with a failure to respond favorably to the selected therapy is identified, along with its expression products, as a screening target for mimics or activators which may be used to improve treatment of said selected condition with said selected therapy.

6 more elements

A method for identifying genes and their expression products as screening targets for modulators which may be used to improve treatment of a selected condition with a selected therapy comprising:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the selected therapy;
(b) determining the expression level of said one or more genes in a second sample from said patient following said treatment with the selected therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to identify genes whose expression level is significantly changed following treatment with the selected therapy;
(d) repeating steps (a)-(c) for each patient in a population of patients affected by the selected condition;
and
(e) determining which patients responded favorably to the selected therapy and which patients did not respond favorably to the selected therapy;
and
(f) comparing the genes whose expression level is significantly changed following treatment with the selected therapy in patients who responded favorably to the selected therapy with the genes whose expression level is significantly changed following treatment with the selected therapy in patients who did not respond favorably to the selected therapy, to thereby identify genes whose expression levels changed in patients who responded favorably to the selected therapy but whose expression levels did not change in patients who did not respond favorably to the selected therapy;
wherein a gene whose expression level following the selected therapy is significantly different in patients who responded favorably compared to patients who did not respond favorably to the selected therapy is identified, along with its expression products, as a screening target for modulators which may be used to improve treatment of said selected condition with said selected therapy.

6 more elements

A method for predicting whether a first therapy will have increased therapeutic efficacy in a patient in comparison with a second therapy, said method comprising the steps of:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the first therapy wherein increased expression of said one or more genes after treatment is correlated with a favorable response to treatment;
(b) determining the expression level of said one or more genes in a second sample from the patient of (a) following said treatment with the first therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to determine the change in the expression level of said genes following treatment with the first therapy;
(d) repeating steps (a), (b), and (c) for each patient in a population of patients affected by the selected condition and treated with the first therapy;
and
(e) determining the expression level of said one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the second therapy;
(f) determining the expression level of said one or more genes in a second sample from the patient of (e) following said treatment with the second therapy;
(g) for each of said one or more genes, comparing the expression level measured in step (e) with the expression level measured in step (f) to determine the change in the expression level of said genes following treatment with the selected therapy;
(h) repeating steps (e), (f), and (g) for each patient in a population of patients affected by the selected condition and treated with the second therapy;
and
(i) for each of said one or more genes, comparing the change in expression level following treatment with the first therapy with the change in expression level following treatment with the second therapy to thereby determine whether the expression levels of said one or more genes show a greater increase in expression levels following treatment with said first therapy than following treatment with said second therapy;
wherein a greater increase in expression levels for one or more of said genes following treatment with the first therapy in comparison with the expression level for said one or more genes following treatment with the second therapy results in a prediction that the first therapy will have increased therapeutic efficacy in a patient in comparison with the second therapy.

9 more elements

A method for predicting whether a first therapy will have increased therapeutic efficacy in a patient in comparison with a second therapy, said method comprising the steps of:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the first therapy, wherein decreased expression of said one or more genes after treatment is correlated with a favorable response in a patient to treatment;
(b) determining the expression level of said one or more genes in a second sample from the patient of (a) following said treatment with the first therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to determine the change in the expression level of said genes following treatment with the selected therapy;
(d) repeating steps (a), (b), and (c) for each patient in a population of patients affected by the selected condition;
and
(e) determining the expression level of said one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the second therapy;
(f) determining the expression level of said one or more genes in a second sample from the patient of (e) following said treatment with the second therapy;
(g) for each of said one or more genes, comparing the expression level measured in step (e) with the expression level measured in step (f) to determine the change in the expression level of said genes following treatment with the selected therapy;
(h) repeating steps (e), (f), and (g) for each patient in a population of patients affected by the selected condition;
and
(i) for each of said one or more genes, comparing the change in expression level following treatment with the first therapy with the change in expression level following treatment with the second therapy to thereby determine whether the expression levels of said one or more genes show a greater decrease in expression levels following treatment with said first therapy than following treatment with said second therapy;
wherein a greater decrease in expression levels for one or more of said genes following treatment with the first therapy in comparison with the expression level for said one or more genes following treatment with the second therapy results in a prediction that the first therapy will have increased therapeutic efficacy in a patient in comparison with the second therapy.

9 more elements

A method for predicting whether a first therapy will have increased deleterious effects in a patient in comparison with a second therapy, said method comprising the steps of:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the first therapy, wherein increased expression of said one or more genes after treatment is correlated with deleterious effects in a patient;
(b) determining the expression level of said one or more genes in a second sample from the patient of (a) following said treatment with the first therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to determine the change in the expression level of said genes following treatment with the selected therapy;
(d) repeating steps (a), (b), and (c) for each patient in a population of patients affected by the selected condition;
and
(e) determining the expression level of said one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the second therapy;
(f) determining the expression level of said one or more genes in a second sample from the patient of (e) following said treatment with the second therapy;
(g) for each of said one or more genes, comparing the expression level measured in step (e) with the expression level measured in step (f) to determine the change in the expression level of said genes following treatment with the selected therapy;
(h) repeating steps (e), (f), and (g) for each patient in a population of patients affected by the selected condition;
and
(i) for each of said one or more genes, comparing the change in expression level following treatment with the first therapy with the change in expression level following treatment with the second therapy to thereby determine whether the expression levels of said one or more genes show a greater increase in expression levels following treatment with said first therapy than following treatment with said second therapy;
wherein a greater increase in expression levels for one or more of said genes following treatment with the first therapy in comparison with the expression level for said one or more genes following treatment with the second therapy results in a prediction that the first therapy will have increased deleterious effects in a patient in comparison with a second therapy.

9 more elements

A method for predicting whether a first will have increased deleterious in a patient in comparison with a second therapy, said method comprising the steps of:

(a) determining the expression level of one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the first therapy, wherein decreased expression of said one or more genes after treatment is correlated with deleterious effects in a patient;
(b) determining the expression level of said one or more genes in a second sample from the patient of (a) following said treatment with the first therapy;
(c) for each of said one or more genes, comparing the expression level measured in step (a) with the expression level measured in step (b) to determine the change in the expression level of said genes following treatment with the selected therapy;
(d) repeating steps (a), (b), and (c) for each patient in a population of patients affected by the selected condition;
and
(e) determining the expression level of said one or more genes in a first sample from a patient affected by the selected condition prior to treatment with the second therapy;
(f) determining the expression level of said one or more genes in a second sample from the patient of (e) following said treatment with the second therapy;
(g) for each of said one or more genes, comparing the expression level measured in step (e) with the expression level measured in step (f) to determine the change in the expression level of said genes following treatment with the selected therapy;
(h) repeating steps (e), (f), and (g) for each patient in a population of patients affected by the selected condition;
and
(i) for each of said one or more genes, comparing the change in expression level following treatment with the first therapy with the change in expression level following treatment with the second therapy to thereby determine whether the expression levels of said one or more genes show a greater decrease in expression levels following treatment with said first therapy than following treatment with said second therapy;
wherein a greater decrease in expression levels for one or more of said genes following treatment with the first therapy in comparison with the expression level for said one or more genes following treatment with the second therapy results in a prediction that the first therapy will have increased deleterious effects in a patient in comparison with a second therapy.

9 more elements

Pre-and post therapy gene expression profiling to identify drug targets

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Pre-and post therapy gene expression profiling to identify drug targets

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Abstract

Claims48