Genetic signature of vulnerability to inhibitors of base excision repair (ber) in cancer
AssigneesDignity Health, The Translational Genomics Research Institute
InventorsShwetal V. Mehta, Michael E. Berens, Harshil Dineshkumar Dhruv
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Abstract
The invention relates to the identification of genetic signatures and expression profiles that are a part of the Base Excision Repair (BER) pathway, a major DNA repair pathway that modifies base lesions. In one embodiment, the present invention provides a method of determining responsiveness of treatment by BER inhibitors for malignant glioma by determining the presence of a low level of expression of Apex 1, a low level of expression of Apex 2, and a high level of expression of MPG.
Claims20
A method of treating cancer, the method comprising the steps of:
- (a) obtaining a sample from a subject with cancer;
- (b) assaying the sample for levels of Apex 1, Apex 2, and MPG, relative to levels of Apex 1, Apex 2, and MPG found in non-cancerous cells;
- and
- (c) administering to the subject therapeutically effective amounts of a Base Excision Repair (BER) pathway inhibitor and a DNA-damaging agent when the results of step (b) indicate that the subject has, relative to non-cancerous cells, reduced levels of Apex 1 and Apex 2 and increased levels of MPG.
A method of treating glioblastoma in a subject, the method comprising the steps of:
- (a) assaying in a sample from the subject levels of Apex 1, Apex 2, and MPG, relative to non-cancerous cells;
- and
- (b) administering to the subject therapeutically effective amounts of methoxyamine and at least one DNA-damaging agent selected from the group consisting of radiation and temozolomide.
A method of treating cancer in a subject, the subject having reduced expression levels of Apex 1 and Apex 2 and increased expression levels of MPG, relative to non-cancerous cells, the method comprising the steps of:
- administering to the subject therapeutically effective amounts of a BER pathway inhibitor and at least one DNA-damaging agent.
Dependencies are inferred from the claim text.