Methods of predicting responsiveness to chemotherapeutic agents and selecting treatments
Methods are provided for predicting responsiveness of cancer cells to chemotherapy by measuring the level of phosphorylated Stat or the level of expression of Survivin in a cancer and comparing the level in the cancer cell to the respective level in a control. Also provided are methods of selecting a chemotherapeutic treatment for a subject diagnosed with cancer by measuring the level of phosphorylated Stat or the level of expression of Survivin in a cancer and comparing the level in the cancer cell to the respective level in a control. Kits for performing the methods are also provided. Methods for modulating Survivin-dependent apoptosis in a cancer cell are also disclosed.
1. A method of predicting responsiveness of cancer cells to a chemotherapeutic agent, comprising:
a) measuring the level of phosphorylated Stat3 in a cancer cell;
b) comparing the level of phosphorylated Stat3 in the cancer cell to the level of phosphorylated Stat3 in a control, wherein the level in the cancer cell is increased or not increased compared to the level in the control; and
c) predicting the responsiveness of the cancer cells to the chemotherapeutic agent based on the level of phosphorylated Stat3 in the cancer cell as compared to the level in the control, wherein when the level in the cancer cell is increased, it is indicative of responsiveness to tyrosine kinase inhibitors, and when the level in the cancer cell is not increased, it is indicative of responsiveness to chemotherapeutic agents that induce apoptosis.
2. The method of claim 1 , wherein the cancer cell is obtained from a subject.
3. The method of claim 2 , wherein the subject is human.
4. The method of claim 1 , wherein the cancer cell is selected from the group consisting of a breast cancer cell, a lung cancer cell, an ovarian cancer cell, a head and neck cancer cell, a melanoma cell, a prostate cancer cell, a multiple myeloma cell, a lymphoma cell, a leukemia cell, a gastric cancer cell, an ovary cancer cell, a colon cancer cell, and a pancreatic cancer cell.
5. The method of claim 4 , wherein the cancer cell is a breast cancer cell.
6. The method of claim 4 , wherein the cancer cell is a non-small cell lung cancer cell.
7. The method of claim 1 , wherein the chemotherapeutic agent is selected from the group consisting of alkylating agents, nitrosoureas, antimetabolites, anthracyclines, topoisomerase inhibitors, taxanes, vinca alkaloids, and tyrosine kinase inhibitors.
8. The method of claim 1 , wherein the chemotherapeutic agent is a taxane.
9. The method of claim 8 , wherein the taxane is docetaxel.
10. The method of claim 1 , wherein the chemotherapeutic agent is a tyrosine kinase inhibitor.
11. The method of claim 10 , wherein the tyrosine kinase inhibitor is selected from the group consisting of Stat inhibitors and EGFR inhibitors.
12. The method of claim 1 , wherein the chemotherapeutic agent is doxorubicin.
13. The method of claim 1 , wherein the level of phosphorylated Stat3 is increased in the cancer cell relative to the control and is predictive of responsiveness to tyrosine kinase inhibitors.
14. The method of claim 1 , wherein the level of phosphorylated Stat3 is not increased in the cancer cell relative to the control and is predictive of responsiveness to chemotherapeutic agents that induce apoptosis.
15. The method of claim 1 , wherein the cancer cell is obtained by a method selected from the group consisting of a biopsy and surgical resection.
16. The method of claim 1 , wherein the level of phosphorylated Stat3 is measured by a method selected from the group consisting of immunohistochemistry, electrophoretic mobility shift assay, Western blot and ELISA.
17. The method of claim 1 , wherein the predicted responsiveness is a complete pathologic response.
18. The method of claim 1 , wherein the predicted responsiveness is a complete clinical response.
19. The method of claim 1 , wherein the control is a non-cancerous cell.
20. The method of claim 19 , wherein the non-cancerous cell is obtained from the same subject as the cancer cell.
21. The method of claim 1 , wherein the control is a cancer cell.
22. The method of claim 1 , wherein the control has a known responsiveness to chemotherapeutic agents.