Predictors Of Patient Response To Treatment With EGFR Inhibitors
First Claim
1. A method for predicting the response of a subject diagnosed with EGFR positive cancer to treatment with an EGFR inhibitor, comprising determining the expression level of one or more RNA transcripts or their expression products in a biological sample containing cancer cells obtained from said subject, wherein the RNA transcript is of one or more genes selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1;
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, wherein (a) for every unit of increased expression of one or more genes selected from groups (i), (ii), (iii), (iv), and (v), or the corresponding expression product, said subject is predicted to have an increased likelihood of response to treatment with said EGFR inhibitor; and
(b) for every unit of increased expression of one or more genes selected from group (vi) or group (vii), or the corresponding expression product, said subject is predicted to have a decreased likelihood of response to treatment with said EGFR inhibitor.
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Abstract
The invention concerns genes and gene sets and methods useful in the prediction of the response of a cancer patient to treatment with an epidermal growth factor receptor (EGFR) inhibitor.
47 Citations
61 Claims
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1. A method for predicting the response of a subject diagnosed with EGFR positive cancer to treatment with an EGFR inhibitor, comprising determining the expression level of one or more RNA transcripts or their expression products in a biological sample containing cancer cells obtained from said subject, wherein the RNA transcript is of one or more genes selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1;
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, wherein(a) for every unit of increased expression of one or more genes selected from groups (i), (ii), (iii), (iv), and (v), or the corresponding expression product, said subject is predicted to have an increased likelihood of response to treatment with said EGFR inhibitor; and
(b) for every unit of increased expression of one or more genes selected from group (vi) or group (vii), or the corresponding expression product, said subject is predicted to have a decreased likelihood of response to treatment with said EGFR inhibitor. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 48, 49, 50, 51, 52, 53, 60, 61)
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
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38. A method for preparing a personalized genomics profile for a human patient diagnosed with EGFR-expressing cancer comprising the steps of:
(a) determining in a biological sample containing cancer cells obtained from said patient the expression level of one or more RNA transcripts or their expression products in a biological sample containing cancer cells obtained from said subject, wherein the RNA transcript is of one or more genes selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1;
(iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, and (b) creating a report summarizing the information generated by step (a).- View Dependent Claims (39, 40, 41, 42, 43, 44, 45, 46, 47)
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54. A method of using a gene selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1;
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, or a corresponding gene product, to predict responsiveness of a patient diagnosed with EGFR-expressing cancer to treatment with an EGFR inhibitor, comprising predicting an increased likelihood of responsiveness if the expression level of one or more genes from groups (i)-(v) is elevated in said cancer, and predicting a decreased likelihood of responsiveness if the expression level of one or more genes from group (vi) or group (vii) is elevated in said cancer.
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
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55. A method of predicting the likelihood of responsiveness of a subject diagnosed with an EGFR-expressing cancer to treatment with an EGFR inhibitor, comprising
identifying evidence of elevated expression of one or more genes selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1; - (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, or a corresponding gene product, whereinevidence of elevated expression of one or more genes from groups (i)-(v) indicates that said subject has an increased likelihood of response to treatment with said EGFR inhibitor, and evidence of elevated expression of one or more genes from group (vi) or group (vii) indicates that said subject has a decreased likelihood of response to treatment with said EGFR inhibitor.
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
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56. A report comprising a summary of the normalized expression levels of an RNA transcript or its expression products in a cancer cell obtained from a subject, wherein said RNA transcript is the RNA transcript of a gene or gene set selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1;
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, or a corresponding gene product, wherein evidence of elevated expression of one or more genes from groups (i)-(v) indicates that said subject has an increased likelihood of response to treatment with said EGFR inhibitor, andevidence of elevated expression of one or more genes from group (vi) or group (vii) indicates that said subject has a decreased likelihood of response to treatment with said EGFR inhibitor.
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
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57. A report comprising a prediction of the response of a subject diagnosed with EGFR positive cancer to treatment with an EGFR inhibitor based on a determination of the normalized expression levels of an RNA transcript or its expression products in a cancer cell obtained from said subject, wherein said RNA transcript is the RNA transcript of a gene or gene set selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1;
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, or a corresponding gene product, wherein evidence of elevated expression of one or more genes from groups (i)-(v) indicates that said subject has an increased likelihood of response to treatment with said EGFR inhibitor, andevidence of elevated expression of one or more genes from group (vi) or group (vii) indicates that said subject has a decreased likelihood of response to treatment with said EGFR inhibitor. - View Dependent Claims (58)
- (iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
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59. A method of producing a report including gene expression information about a cancer cell obtained from a subject comprising the steps of:
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(a) determining normalized expression levels of an RNA transcript or its expression products in a cancer cell obtained from said subject, wherein said RNA transcript is the RNA transcript of a gene or gene set selected from the group consisting of (i) genes located near EGFR on chromosome 7p11.2, (ii) ERBB2 and genes located near ERBB2 on chromosome 12q.13, (iii) ERBB3 and genes located near ERBB3 on chromosome 17q21.1;
(iv) ERBB4 and genes located near ERBB4 on chromosome 7p11.2;
(v) genes involved in ADCC and gene markers of immune or inflammatory cells;
(vi) genes associated with tumor cell invasion; and
(vii) genes characteristic of late stage tumors, or a corresponding gene product, wherein evidence of elevated expression of one or more genes from groups (i)-(v) indicates that said subject has an increased likelihood of response to treatment with said EGFR inhibitor, andevidence of elevated expression of one or more genes from group (vi) or group (vii) indicates that said subject has a decreased likelihood of response to treatment with said EGFR inhibitor.; and
(b) creating a report summarizing said information.
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Specification