Methods of treating cancer sensitive to anti-egfr therapy and modifying treatment using blood biomarkers
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsEdwin Chang, Lingyun Xu, Nick Hughes, Carsten H. Nielsen, Sanjiv S. Gambhir, Parag Mallick, Arutselvan Natarajan
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Abstract
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.
Claims33
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 subject having a cancer predicted to be sensitive to anti-epidermal growth factor receptor (EGFR) treatment;
- initiating a treatment regimen for the subject with an anti-EGFR drug, the treatment comprising administering one or more doses of the anti-EGFR drug to the subject 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 initial treatment with the 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 anti-EGFR treatment regimen;
- optionally determining one or more subsequent levels of PRDX6 in samples taken from the subject after the second sample;
- updating the PRDX6 expression profile for the subject to include any subsequent PRDX6 levels;
- using the PRDX6 expression profile to evaluate efficacy of the anti-EGRF drug in reducing tumor volume;
- and
- continuing, modifying, or discontinuing the treatment regimen with the anti-EGFR drug based on the PRDX6 expression profile.
A method of determining sensitivity or resistance of a cancer in a subject to an anti-epidermal growth factor receptor (EGFR) drug, the method comprising:
- determining a pre-treatment level of peroxiredoxin 6 (PRDX6) protein in a sample taken from a subject having cancer;
- providing one or more doses of an anti-epidermal growth factor receptor (EGFR) drug to the subject over a period of time;
- determining a second level of PRDX6 in a sample taken from the subject no later than about 4 weeks after an initial treatment with the anti-EGFR drug;
- creating a PRDX6 expression profile comparing the pre-treatment level of PRDX6 with the second level of PRDX6, relative to the anti-EGFR treatment regimen;
- and
- determining sensitivity or potential non-responsiveness or resistance of the cancer to the anti-EGFR drug based on the PRDX6 expression profile.
An in vitro method of determining sensitivity or resistance of a cancer in a subject to an anti-epidermal growth factor receptor (EGFR) drug, the method comprising:
- obtaining a biopsy sample of cancer cells from a subject;
- growing the cancer cells in culture;
- determining a level of peroxiredoxin 6 (PRDX6) protein produced by the cells;
- exposing the cancer cells to the anti-EGFR drug;
- determining a second level of PRDX6 protein produced by the cells between about 10 and about 24 hours after exposing the cells to the anti-EGFR drug;
- creating a PRDX6 expression profile for the cells comparing the first level of PRDX6 to the second level of PRDX6;
- determining sensitivity of the cancer to the anti-EGFR drug, resistance of the cancer to the anti-EGFR drug, or an inconclusive result, based on the PRDX6 expression profile.
A cancer sensitivity assay comprising:
- a sample of cancer cells obtained from a subject;
- culture medium for growing the cells;
- an anti-epidermal growth factor receptor (EGFR) drug used for treatment of cancer;
- a capture antibody specific for peroxiredoxin 6 (PRDX6) protein;
- and
- a detection antibody capable of binding PRDX6.
A cancer sensitivity assay comprising:
- a sample obtained from a subject having a cancer predicted to be sensitive to anti-epidermal growth factor receptor (EGFR) treatment, wherein the sample is taken before initiation of an anti-EGFR treatment regimen with an anti-EGFR drug or sometime during the anti-EGFR treatment regimen;
- a capture antibody specific for peroxiredoxin 6 (PRDX6) protein;
- and
- a detection antibody capable of binding PRDX6.
Dependencies are inferred from the claim text.