Methods for predicting responsiveness of a cancer cell to an anti-IGFR1 antibody by analysis of mutations in PIK3CA
The present disclosure relates generally to methods and materials for determining the responsiveness of a subject with a disease or disorder to an inhibitor of a receptor tyrosine kinase including, for example, IGF1R. Such methods may comprise obtaining a biological sample from the subject, assaying the biological sample for one or more PIK3CA mutations, determining if one or more PIK3CA mutations are present in the biological sample, and employing the determination of one or more PIK3CA mutations in the biological sample to predict responsiveness of the subject to the receptor tyrosine kinase inhibitor.
1. A method of contacting a cell with an antibody specific for insulin-like growth factor 1 receptor (IGF1R), the method comprising:
a. obtaining a cell;
b. assaying the cell for one or more PIK3CA mutations;
c. determining if one or more PIK3CA mutations are present in the cell;
d. employing the determination of one or more PIK3CA mutations in the cell to predict responsiveness of the cell to the antibody, wherein the presence of one or more PIK3CA mutations in the cell predicts that the cell will be responsive to the antibody; and
e. selectively contacting a cell predicted to be responsive to the antibody with the antibody.
2. The method of claim 1 , wherein PIK3CA has the amino acid sequence set forth in SEQ ID NO: 1.
3. The method of claim 2 , wherein the one or more mutations in PIK3CA are selected from the group consisting of: E542K, E545K, E545G, E545D, Q546K, Q546R, M1043I, M1043V, H1047R, H1047L, H1047Y, G1049R and G1049S.
4. The method of claim 1 , wherein the cell is assayed for PIK3CA mutations by analyzing nucleic acid obtained from the cell.
5. The method of claim 1 , wherein the antibody is a monoclonal antibody.
6. The method of claim 1 , wherein the cell is from a tumor biopsy.
7. The method of claim 1 , wherein the cell is from an aspirate.
8. The method of claim 1 , wherein the cell is from a cancer patient.
9. A method for treating a subject with cancer with an antibody specific for IGF1R, the method comprising:
a. obtaining a biological sample from the subject;
b. assaying the biological sample for one or more PIK3CA mutations;
c. determining if one or more PIK3CA mutations are present in the biological sample;
d. employing the determination of one or more PIK3CA mutations in the cell to predict responsiveness of the subject to the antibody, wherein the presence of one or more PIK3CA mutations in the biological sample predicts that the subject will be responsive to the antibody; and
e. administering a therapeutically effective amount of the antibody to the subject predicted to be responsive to the IGF1R antibody with the antibody to treat the cancer.
10. The method of claim 9 , wherein PIK3CA has the amino acid sequence set forth in SEQ ID NO: 1.
11. The method of claim 10 , wherein the one or more mutations in PIK3CA are selected from the group consisting of: E542K, E545K, E545G, E545D, Q546K, Q546R, M1043I, M1043V, H1047R, H1047L, H1047Y, G1049R and G1049S.
12. The method of claim 9 , wherein the biological sample is assayed for PIK3CA mutations by analyzing nucleic acid obtained from the sample.
13. The method of claim 9 , wherein the biological sample is assayed for PIK3CA mutations by analyzing proteins obtained from the sample.
14. The method of claim 12 , wherein the cancer is breast cancer.
15. The method of claim 9 , wherein the antibody is a monoclonal antibody.
16. The method of claim 9 , wherein the biological sample is a tumor biopsy.
17. The method of claim 9 , wherein the biological sample is an aspirate.
18. A method for selecting a subject with cancer for treatment with an antibody specific for IGF1R, the method comprising:
a. obtaining a biological sample from the subject;
b. assaying the biological sample for one or more PIK3CA mutations;
c. determining if one or more PIK3CA mutations are present in the biological sample;
d. employing the determination of one or more PIK3CA mutations in the cell to predict responsiveness of the subject to the antibody, wherein the presence of one or more PIK3CA mutations in the biological sample predicts that the subject will be responsive to the antibody; and
e. selecting the subject predicted to be responsive to the IGF1R antibody for treatment with a therapeutically effective amount of the antibody.
19. The method of claim 18 , wherein PIK3CA has the amino acid sequence set forth in SEQ ID NO: 1.
20. The method of claim 19 , wherein the one or more mutations in PIK3CA are selected from the group consisting of: E542K, E545K, E545G, E545D, Q546K, Q546R, M1043I, M1043V, H1047R, H1047L, H1047Y, G1049R and G1049S.
21. The method of claim 18 , wherein the biological sample is assayed for PIK3CA mutations by analyzing nucleic acid obtained from the sample.
22. The method of claim 18 , wherein the biological sample is assayed for PIK3CA mutations by analyzing proteins obtained from the sample.
23. The method of claim 18 , wherein the cancer is breast cancer.
24. The method of claim 18 , wherein the antibody is a monoclonal antibody.
25. The method of claim 18 , wherein the biological sample is a tumor biopsy.
26. The method of claim 18 , wherein the biological sample is an aspirate.