Methods of evaluating patients using E-cadherin and vimentin
Methods for the selection, evaluation, and/or treatment of a patient having cancer with an inhibitor of a glutamine-utilizing enzyme or a glutamine-depleting agent, by evaluating E-cadherin or vimentin expression are disclosed.
1. A method of treating a patient having cancer, the method comprising:
acquiring an evaluation of or evaluating a patient sample, wherein the sample is evaluated for i) E-cadherin expression levels and ii) vimentin expression levels; and
if E-cadherin expression levels are low, and vimentin expression levels are high, as compared to a reference standard, then
administering to the patient in need thereof a therapeutically effective amount of an inhibitor of a glutamine-utilizing enzyme or a glutamine-depleting agent.
2. The method of claim 1 , wherein the sample is evaluated for low or decreased pyruvate carboxylase expression compared to a reference standard.
3. The method of claim 1 , wherein the level of E-cadherin expression is at least a 1.5, 2, 5, 10, 15, 20, 25, 50, 75, 100 fold decrease in expression compared to the reference standard.
4. The method of claim 1 , wherein the level of vimentin expression is a 1.5, 2, 5, 10, 15, 20, 25, 50, 75, 100 fold increase compared to the reference standard.
5. The method of claim 1 , wherein the level of E-cadherin expression is measured by the evaluation of the level of RNA that encodes E-cadherin.
6. The method of claim 1 , wherein the level of vimentin expression is measured by the evaluation of the level of RNA that encodes vimentin.
7. The method of claim 1 , wherein the level of E-cadherin expression is evaluated by the level of E-cadherin protein expression.
8. The method of claim 1 , wherein the level of vimentin expression is evaluated by the level of vimentin protein expression.
9. The method of claim 1 , wherein the patient is administered a therapeutically effective amount of an inhibitor of a glutamine-utilizing enzyme.
10. The method of claim 9 , wherein the inhibitor of a glutamine-utilizing enzyme inhibits a glutaminase.
11. The method of claim 10 , wherein the glutaminase is GLS1 or glutaminase C(GAC).
12. The method of claim 11 , wherein the inhibitor is bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES).
13. The method of claim 1 , wherein the patient is administered a therapeutically effective amount of a glutamine depleting agent.
14. The method of claim 13 , wherein the glutamine depleting agent is an asparaginase or a glutaminase.
15. The method of claim 1 , wherein the cancer is lung cancer.
16. The method of claim 15 , wherein the lung cancer is non-small cell lung cancer.
17. A method of evaluating a patient having cancer for treatment with an inhibitor of glutamine-utilizing enzyme or a glutamine-depleting agent, the method comprising:
evaluating a patient sample, wherein the sample is evaluated for i) a low level of E-cadherin expression compared to a reference standard and ii) a high level of vimentin expression compared to a reference standard; and
determining to treat the patient with the inhibitor of glutamine-utilizing enzyme or the glutamine-depleting agent.
18. The method of claim 17 , wherein the sample is evaluated for low or decreased pyruvate carboxylase expression compared to a reference standard.
19. The method of claim 17 , wherein the level of E-cadherin expression is at least a 1.5, 2, 5, 10, 15, 20, 25, 50, 75, 100 fold decrease in expression compared to the reference standard.
20. The method of claim 17 , wherein the level of vimentin expression is a 1.5, 2, 5, 10, 15, 20, 25, 50, 75, 100 fold increase compared to the reference standard.
21. The method of claim 17 , wherein the level of E-cadherin expression is measured by the evaluation of the level of RNA that encodes E-cadherin.
22. The method of claim 17 , wherein the level of vimentin expression is measured by the evaluation of the level of RNA that encodes vimentin.
23. The method of claim 17 , wherein the level of E-cadherin expression is evaluated by the level of E-cadherin protein expression.
24. The method of claim 17 , wherein the level of vimentin expression is evaluated by the level of vimentin protein expression.
25. The method of claim 17 , wherein the patient is evaluated for treatment with an inhibitor of a glutamine-utilizing enzyme.
26. The method of claim 25 , wherein the inhibitor of a glutamine-utilizing enzyme inhibits a glutaminase.
27. The method of claim 26 , wherein the glutaminase is GLS1 or glutaminase C(GAC).
28. The method of claim 26 , wherein the inhibitor is bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES).
29. The method of claim 17 , wherein the patient is administered a therapeutically effective amount of a glutamine depleting agent.
30. The method of claim 29 , wherein the glutamine depleting agent is an asparaginase or a glutaminase.
31. The method of claim 17 , wherein the cancer is lung cancer.
32. The method of claim 31 , wherein the lung cancer is non-small cell lung cancer.