Methods of treating cancer sensitive to anti-EGFR therapy and modifying treatment using peroxiredoxin 6 biomarker

摘要

The present disclosure provides methods of treating cancer and modifying a cancer treatment for a cancer with an anti-EGFR drug by creating PRDX6 expression profiles and using the profiles to evaluate and optionally modify treatment. The present disclosure also provides assays and systems for assessing sensitivity of a cancer to an anti-EGFR therapy.

主权项

1. A method of treating cancer in a subject, the method comprising:
determining a pre-treatment level of peroxiredoxin 6 (PRDX6) protein in a sample taken from a human subject having a cancer predicted to be sensitive to anti-epidermal growth factor receptor (EGFR) treatment, the cancer comprising cells with an EGFR mutation, wherein the pre-treatment sample is taken from the subject before or at the time of initiation of treatment with a tyrosine kinase inhibitor (TKI) anti-EGFR drug;
initiating a treatment regimen for the subject with a TKI anti-EGFR drug, wherein the subject receives one or more doses of the TKI anti-EGFR drug over a period of time;determining a second level of PRDX6 in a second sample taken from the subject no later than about 4 weeks after the subject takes the initial dose of the TKI anti-EGFR drug;creating a PRDX6 expression profile for the subject, wherein the PRDX6 expression profile compares the pre-treatment and second PRDX6 levels relative to the TKI anti-EGFR treatment regimen; andcontinuing, modifying, or discontinuing the treatment regimen with the TKI anti-EGFR drug based on the PRDX6 expression profile, wherein:treatment with the anti-EGFR drug is continued when the second level is at least 10% greater than the pre-treatment level of PRDX6 for the subject, indicating sensitivity to the anti-EGFR drug, ortreatment with the anti-EGFR drug is either discontinued or is continued by maintaining the dosage of the anti-EGFR drug or by increasing the amount of the drug subsequently administered to the subject when the second level is about the same as the pre-treatment level, about 10% less than the pre-treatment level, or less than about 10% greater than the pre-treatment level of PRDX6 for the subject, indicating potential non-responsiveness or resistance, andoptionally determining one or more subsequent levels of PRDX6 in subsequent samples taken from the subject after the second sample, wherein the pre-treatment sample, second sample and any subsequent samples comprise a sample selected from the group consisting of: blood, plasma, and sera; andupdating the PRDX6 expression profile for the subject to include any subsequent PRDX6 levels for evaluation of efficacy of the TKI anti-EGRF drug in reducing tumor volume.