Non-invasive functional companion assays for oncogene targeted therapy for brain cancer

A method of identifying a metabolic process inhibitor as an effective treatment for a glioblastoma, the method comprising:

• administering to a subject in need thereof the metabolic process inhibitor
• administering to the subject a substrate for a metabolic process, wherein the substrate is detectably labeled;
• and
• measuring the amount of the detectably labeled substrate in the glioblastoma after administering the metabolic process inhibitor, wherein a decrease in the amount of detectably labeled substrate relative to a reference level indicates that the glioblastoma is a metabolic responder to the inhibitor;
• and
• if the glioblastoma is identified as a metabolic responder, treating the subject with the metabolic process inhibitor for a period of time and imaging the glioblastoma to assess a change tumor volume over the period of time, wherein a decrease in tumor volume identifies the inhibitor as an effective treatment for the glioblastoma.

A method of treating a glioblastoma, the method comprising:

• administering to a subject having a glioblastoma a first dose of an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI);
• administering to the subject a substrate for a metabolic process, wherein the substrate has an exchangeable proton;
• detecting a pH change in the glioblastoma after administering the EGFR TKI, wherein an increase in the pH relative to a reference level indicates that the glioblastoma is a metabolic responder to the inhibitor;
• and
• if the pH is greater than the reference level, treating the subject with the EGFR TKI for a period of time and imaging the glioblastoma to assess a change in tumor volume over the period of time.

A method of identifying a metabolic process inhibitor as an effective treatment for a glioblastoma, the method comprising:

• administering to a subject in need thereof the metabolic process inhibitor administering to the subject a substrate for a metabolic process;
• and
• measuring the pH in the glioblastoma after administering the metabolic process inhibitor, wherein an increase in the pH relative to a reference level indicates that the glioblastoma is a metabolic responder to the inhibitor;
• and
• if the glioblastoma is identified as a metabolic responder, treating the subject with the metabolic process inhibitor for a period of time and imaging the glioblastoma to assess a change tumor volume over the period of time, wherein a decrease in tumor volume identifies the inhibitor as an effective treatment for the glioblastoma.

A method of monitoring a glioblastoma tumor in a subject receiving an EGFR TKI therapy, the method comprising:

• assessing the size or volume of the glioblastoma tumor at a first time point;
• assessing the size or volume of the glioblastoma tumor at at least one subsequent time point, wherein the patient has received at least one dose of the therapy between the first and the at least one subsequent time point;
• and
• comparing the sizes or volumes of the glioblastoma tumor at the first time point and at the at least one subsequent time point, wherein a decrease in tumor size or volume at a subsequent time point relative to the first time point indicates the therapy is effective.

The use of an EGFR tyrosine kinase inhibitor (TKI) in the manufacture of a medicament for the treatment of a glioblastoma tumor according to a method wherein the effectiveness of the treatment is determined by:

• a) assessing the size or volume of the glioblastoma tumor at a first time point;
• b) assessing the size or volume of the glioblastoma tumor at at least one subsequent time point;
• and
• c) comparing the sizes or volumes of the glioblastoma tumor at the first time point and at the at least one subsequent time point, wherein a decrease in tumor size or volume at a subsequent time point relative to the first time point indicates the treatment is effective.

Use of an EGFR tyrosine kinase inhibitor (TKI) for the treatment of a glioblastoma tumor according to a method that comprises:

• a) assessing the size or volume of the glioblastoma tumor at a first time point during the treatment;
• b) assessing the size or volume of the glioblastoma tumor at at least one subsequent time point during the treatment;
• and
• c) comparing the sizes or volumes of the glioblastoma tumor at the first time point and the at least one subsequent time point, wherein a decrease in tumor size or volume at a subsequent time point relative to the first time point indicates the treatment is effective.

A method of treating a glioblastoma, the method comprising:

• identifying a polysomy in a glioblastoma tumor;
• administering to a subject having a glioblastoma a first dose of an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI);
• administering to the subject a detectably labeled substrate for a metabolic process;
• measuring an amount of the detectably labeled substrate in the glioblastoma after administering the EGFR TKI, wherein a decrease in the amount of detectably labeled substrate relative to a reference level indicates that the glioblastoma is a metabolic responder to the inhibitor;
• and
• if the measured amount is less than the reference level, treating the subject with the EGFR TKI for a period of time and imaging the glioblastoma to assess a change in tumor volume over the period of time.