Genetic signature of vulnerability to inhibitors of base excision repair (ber) in cancer
AssigneesThe Translational Genomics Research Institute, Dignity Health
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.
Claims38
A method of treating a cancer in a subject, comprising:
- obtaining a sample from the subject;
- assaying the sample to determine the expression levels of Apex 1, Apex 2, and MPG relative to levels found in a non-tumor cell,
- wherein a low level of Apex 1, a low level of Apex 2, and a high level of MPG relative to levels found in a non-tumor cell is indicative of responsiveness to a cancer therapeutic;
- and
- treating the subject.
4-8. (canceled)
10-11. (canceled)
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16-17. (canceled)
A method of treating a cancer in a subject, comprising:
- obtaining a sample;
- assaying the sample to determine the presence of one or more Base Excision Repair (BER) pathway markers;
- and
- treating the subject.
25-26. (canceled)
A method of diagnosing a cancer in a subject, comprising:
- obtaining a sample;
- assaying the sample to determine the presence or absence of one or more Base Excision Repair (BER) pathway markers;
- and
- diagnosing the disease based on the presence of one or more BER pathway markers in the subject.
A method treating a subject, comprising:
- determining the presence of a pattern of Base Excision Repair (BER) pathway markers;
- identifying one or more inhibitors to one of the BER genes that would benefit the patient based on the pattern;
- and
- administering a therapeutically effective dosage of the one or more inhibitors to the subject.
A kit, comprising a panel of one or more Base Excision Repair (BER) pathway markers.
43-44. (canceled)
A method of drug discovery, comprising:
- determining the presence of a pattern of gene expression and/or protein abundance from one or more genes involved in Base Excision Repair (BER);
- and
- preparing one or more suitable inhibitors of BER genes based on the pattern of gene expression and/or protein abundance.
Dependencies are inferred from the claim text.