Gene Expression Markers for Response to EGFR Inhibitor Drugs
OwnerDavid Agus, Steven Shak +2inventors
InventorsDavid Agus, Steven Shak, Maureen Cronin, Joffre Baker
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Abstract
The present invention concerns prognostic markers associated with cancer. In particular, the invention concerns prognostic methods based on the molecular characterization of gene expression in paraffin-embedded, fixed samples of cancer tissue, which allow a physician to predict whether a patient is likely to respond well to treatment with an EGFR inhibitor.
Claims53
A method for predicting the likelihood that a patient who is a candidate for treatment with an EGFR inhibitor will respond to said treatment, comprising determining the expression level of the transcript of STAT5B, or its expression product, in cancer cells obtained from said patient, wherein over-expression of the transcript of STAT5B normalized relative to the mean level of the RNA transcripts, or the corresponding expression products, in a cancer tissue reference set of at least 30 cancer tissue specimens or the product of two or more reference normalizing genes, indicates that said treatment-is not likely to provide a benefit to the patient.
An array comprising polynucleotides hybridizing to the following genes:
- STAT5A, STAT5B, WISP1, CKAP4, FGFr1, cdc25A, RASSF1, G-Catenin, H2AFZ, NME1, NRG1, BC12, TAGLN, YB1, Src, IGF1R, CD44, DIABLO, TIMP2, PDGFrA, CTSB, Hepsin, ErbB3, MTA, Gus, and VEGF, immobilized on a solid surface.
An array comprising polynucleotides hybridizing to the following genes:
- STAT5A, STAT5B, WISP1, CKAP4, FGFR1, cdc25A, RASSF1, G-Catenin, H2AFZ, NME1, NRG1, BC12, TAGLN, YB1, Src, IGF1R, CD44, DIABLO, TIMP2, PDGFRa, and CTSB.
An array comprising polynucleotides hybridizing to the following genes:
- Hepsin, ErbB3, MTA, Gus, and VEGF.
A method of preparing a personalized genomics profile for a patient, comprising the steps of;
- (a) subjecting RNA extracted from cancer cells obtained from the patient to gene expression analysis;
- (b) determining the expression level in the cancer cells of STAT5B, normalized relative to the mean level of the RNA transcripts in a cancer tissue reference set of at least 30 cancer tissue specimens or the product of two or more reference normalizing genes;
- and
- (c) creating a report summarizing the data obtained by said gene expression analysis.
The method of claim 30 wherein the cancer cells are lung cancer.
A method for amplification of a gene selected from the group consisting of STAT5A, STAT5B, WISP1, CKAP4, FGFr1, cdc25A, RASSF1, G-Catenin, H2AFZ, NME1, NRG1, BC12, TAGLN, YB1, Src, IGF1R, CD44, DIABLO, TIMP2, PDGFRA, CTSB, Hepsin, ErbB3, MTA, Gus, and VEGF by polymerase chain reaction (PCR), comprising performing said PCR by using a corresponding amplicon listed in Table 3, and a corresponding primer-probe set listed in Table 4.
A PCR primer-probe set listed in Table 4.
A PCR amplicon listed in Table 3.
A prognostic method comprising:
- (a) subjecting a sample comprising cancer cells obtained from a patient to quantitative analysis of the expression level of the RNA transcript of STAT5B, or its products, and
- (b) identifying the patient as not likely to benefit from treatment with an EGFR inhibitor if the expression levels of said STAT5B RNA transcript or its products normalized relative to the mean level of the RNA transcripts or their products in a cancer tissue reference set of at least 30 cancer tissue specimens or the product of two or more reference normalizing genes, are elevated above a defined expression threshold.
Dependencies are inferred from the claim text.