COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TREATMENT OF CANCER
Provided herein are methods and compositions useful in the diagnosis and treatment of cancer. The methods and compositions typically involve detecting a level of phosphorylation of mTOR at serine 2481 in a subject and comparing the level of phosphorylation of mTOR at serine 2481 in said subject with a standard control.
1 . A method of predicting whether a subject that has a cancer would be responsive to an mTOR inhibition cancer treatment, said method comprising:
(i) detecting a level of phosphorylation of mTOR at serine 2481 in said subject;
(ii) comparing the level of phosphorylation of mTOR at serine 2481 in said subject with a standard control, wherein a high level of phosphorylation of mTOR at serine 2481 in said subject relative to said standard control indicates said subject would be responsive to an mTOR inhibition cancer treatment.
2 . A method of monitoring progression of a cancer in a subject that has said cancer, said method comprising:
(i) detecting a level of phosphorylation of mTOR at serine 2481 in said subject;
(ii) comparing the level of phosphorylation of mTOR at serine 2481 in said subject with a standard control, wherein a high level of phosphorylation of mTOR at serine 2481 in said subject relative to said standard control indicates a higher progression of cancer in said subject.
3 . A method of determining whether a subject is at risk of developing a cancer, said method comprising:
(i) detecting a level of phosphorylation of mTOR at serine 2481 in said subject;
(ii) comparing the level of phosphorylation of mTOR at serine 2481 in said subject with a standard control, wherein a high level of phosphorylation of mTOR at serine 2481 in said subject relative to said standard control indicates said subject is at risk of developing said cancer.
4 . A method of determining whether a subject has a cancer, said method comprising:
(i) detecting a level of phosphorylation of mTOR at serine 2481 in said subject;
(ii) comparing the level of phosphorylation of mTOR at serine 2481 in said subject with a standard control, wherein a high level of phosphorylation of mTOR at serine 2481 in said subject relative to said standard control indicates said subject has said cancer.
5 . The method of one of claim 1 , 2 , 3 or 4 , wherein said detecting the level of phosphorylation of mTOR at serine 2481 in said subject comprises detecting a level of phosphorylation of mTOR at serine 2481 in a sample from said subject.
6 . The method of claim 5 , wherein said detecting the level of phosphorylation of mTOR at serine 2481 in said subject comprises contacting said sample with an anti-S2481 antibody.
7 . The method of one of claim 1 , 2 , 3 or 4 , wherein said cancer is breast cancer or lung cancer.
8 . The method of one of claim 1 , 2 , 3 or 4 , wherein said standard control is a level of phosphorylation of mTOR at serine 2481 in said subject at an earlier time point.
9 . The method of one of claim 1 , 2 , 3 or 4 , wherein said standard control is an average level of phosphorylation of mTOR at serine 2481 derived from a plurality of control subjects.
10 . The method of claim 1 , wherein said mTOR inhibition cancer treatment is a treatment with rapamycin, Ku-0063794, PP242, PP30, Torin1 or analogs thereof.
11 . A method of determining whether a test compound is a cancer therapeutic, said method comprising:
(i) contacting said test compound with a cell;
(ii) detecting a level of phosphorylation of mTOR at serine 2481 in said cell;
(iii) comparing said level of phosphorylation of mTOR at serine 2481 to a standard control, wherein a high level of phosphorylation of mTOR at serine 2481 in said cell relative to said standard control indicates said test compound is a cancer therapeutic.
12 . The method of claim 11 , wherein said standard control is a level of phosphorylation of mTOR at serine 2481 in said cell in the absence of said test compound.