Diagnostic methods and compositions for treatment of cancer

A method of optimizing therapeutic efficacy of an anti-cancer therapy for a patient, the method comprising:

• (a) detecting expression of at least one of the following genes, DLL4, angiopoietin 2 (Angpt2), NOS2, Factor V, Factor VIII (AHF), EGFL7, EFNA3, PGF, ANGPTL1, SELP, Cox2, Fibronectin (FN_EIIIB), ESM1, and stromal derived growth factor (SDF1), in a biological sample obtained from the patient prior to any administration of a VEGF antagonist to the patient;
• (b) comparing the expression level of the at least one gene to a reference expression level of the at least one gene, wherein a change in the level of expression of the at least one gene in the patient sample relative to the reference level identifies a patient who is likely to respond to treatment with a VEGF antagonist;
• and
• (c) providing a recommendation to the patient that the anti-cancer therapy comprise a VEGF antagonist.

A method of monitoring whether a patient who has received at least one dose of a VEGF antagonist will respond to treatment with a VEGF antagonist, the method comprising:

• (a) detecting expression of at least one of the following genes, DLL4, angiopoietin 2 (Angpt2), NOS2, Factor V, Factor VIII (AHF), EGFL7, EFNA3, PGF, ANGPTL1, SELP, Cox2, Fibronectin (FN_EIIIB), ESM1, and stromal derived growth factor (SDF1), in a biological sample obtained from the patient following administration of the at least one dose of a VEGF antagonist;
• (b) comparing the expression level of the at least one gene to a reference level, which is the expression level of the at least one gene in a biological sample obtained from the patient prior to administration of the VEGF antagonist to the patient, wherein a change in the expression level of the at least one gene in the sample obtained following administration of the VEGF antagonist relative to the reference level identifies a patient who will respond to treatment with a VEGF antagonist;
• and
• (c) informing the patient that they have an increased likelihood of being responsive to treatment with a VEGF antagonist.

A method for selecting a therapy for a particular patient in a population of patients being considered for therapy, the method comprising:

• (a) detecting expression of at least one of the following genes, DLL4, angiopoietin 2 (Angpt2), NOS2, Factor V, Factor VIII (AHF), EGFL7, EFNA3, PGF, ANGPTL1, SELP, Cox2, Fibronectin (FN_EIIIB), ESM1, and stromal derived growth factor (SDF1), in a biological sample obtained from the patient prior to any administration of a VEGF antagonist to the patient;
• (b) comparing the expression level of the at least one gene to a reference expression level of the at least one gene, wherein a change in the level of expression of the at least one gene in the patient sample relative to the reference level identifies a patient who is likely to respond to treatment with a VEGF antagonist;
• and
• (c) selecting a therapy comprising a VEGF antagonist if the patient is identified as likely to respond to treatment with a VEGF antagonist and recommending to the patient the selected therapy comprising a VEGF antagonist;
• or
• (d) selecting a therapy that does not comprise a VEGF antagonist if the patient is not identified as likely to respond to treatment with a VEGF antagonist and recommending to the patient the selected therapy that does not comprise a VEGF antagonist.

A method for selecting a therapy for a patient who has received at least one dose of a VEGF antagonist, the method comprising:

• (a) detecting expression of at least one of the following genes, DLL4, angiopoietin 2 (Angpt2), NOS2, Factor V, Factor VIII (AHF), EGFL7, EFNA3, PGF, ANGPTL1, SELP, Cox2, Fibronectin (FN_EIIIB), ESM1, and stromal derived growth factor (SDF1), in a biological sample obtained from the patient following administration of the VEGF antagonist;
• (b) comparing the expression level of the at least one gene to a reference level, which is the expression level of the at least one gene in a biological sample obtained from the patient prior to administration of the VEGF antagonist to the patient, wherein a change in the level of to expression of the at least one gene in the patient sample relative to the reference level identifies a patient who is likely to respond to treatment with a VEGF antagonist, and
• (c) selecting a therapy comprising a VEGF antagonist if a change in the expression level of the at least one gene is detected in the sample obtained following administration of the VEGF antagonist and recommending to the patient the selected therapy comprising a VEGF antagonist;
• or
• (d) selecting a therapy that does not comprise a VEGF antagonist if no change in the expression level of the at least one gene is detected in the sample obtained following administration of the VEGF antagonist and recommending to the patient the selected therapy that does not comprise a VEGF antagonist.

A method for diagnosing an angiogenic disorder in a patient, the method comprising the steps of:

• (a) detecting the expression level of at least one of the following genes, DLL4, angiopoietin 2 (Angpt2), NOS2, Factor V, Factor VIII (AHF), EGFL7, EFNA3, PGF, ANGPTL1, SELP, Cox2, Fibronectin (FN_EIIIB), ESM1, and stromal derived growth factor (SDF1), in a sample obtained from the patient prior to any administration of a VEGF antagonist to the patient;
• and
• (b) comparing the expression level of the at least one gene or biomarker to a reference level of the at least one gene, wherein a change in the level of expression of the at least one gene in the patient sample relative to the reference level identifies a patient having an angiogenic disorder;
• and
• (c) informing the patient that they have an angiogenic disorder.

A kit for determining whether a patient may benefit from treatment with a VEGF antagonist, the kit comprising:

• (a) polypeptides or polynucleotides capable of determining the expression level of at least one of the following genes:
• DLL4, angiopoietin 2 (Angpt2), NOS2, Factor V, Factor VIII (AHF), EGFL7, EFNA3, PGF, ANGPTL1, SELP, Cox2, Fibronectin (FN_EIIIB), ESM1, and stromal derived growth factor (SDF1);
• and
• (b) instructions for use of the polypeptides or polynucleotides to determine the expression level of at least one of DLL4, angiopoietin 2 (Angpt2), NOS2, Factor V, Factor VIII (AHF), EGFL7, EFNA3, PGF, ANGPTL1, SELP, Cox2, Fibronectin (FN_EIIIB), ESM1, and stromal derived growth factor (SDF1), wherein a change in the level of expression of the at least one gene relative to a reference level indicates that the patient may benefit from treatment with a VEGF antagonist.