MULTIPLE MECHANISMS FOR MODULATION OF THE PI3 KINASE PATHWAY

• US 20100233733A1
• Filed: 02/10/2010
• Published: 09/16/2010
• Est. Priority Date: 02/10/2009
• Status: Abandoned Application

• Current Assignee: Nodality Inc.
• Original Assignee: Nodality Inc.
• Inventors: Fantl, Wendy J.
• Application Number:
  US12/703,741
• Publication Number:
  US 20100233733A1
• Time in Patent Office: Days
• US Class Current: 435/7.230
• CPC Class Codes: C12Q 1/485 involving kinase
• CPC Class Codes: G01N 2333/9121 with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases
• CPC Class Codes: G01N 2800/56 Staging of a disease; Further complications associated with the disease
• CPC Class Codes: G01N 33/5011 for testing antineoplastic activity
• CPC Class Codes: G01N 33/574 for cancer

Abstract

An embodiment of the present invention is a method for measuring the post translational states and expression levels of proteins in the PI3K and/or mTor for use in diagnosis, prognosis and drug screening applications.

Claims

1. A method for classifying a cell comprising:

contacting the cell with a PI3K and/or mTOR pathway modulator;

determining the presence or absence of a change in activation level of an activatable element in the cell; and

classifying the cell based on the presence or absence of the change in the activation level of the activatable element.

2. The method of claim 1, wherein the change in activation level of the activatable element is an increase in activation level of the activatable element.

3. The method of claim 1, wherein the cell is a cancer cell or hematopoietic cell.

4. The method of claim 1, wherein the presence or absence of a change in the activation level of the activatable element is compared to a normal cell contacted with the PI3K and/or mTOR inhibitor.

5. The method of claim 1, wherein the presence or absence of a change in the activation levels of the activatable element is determined in the determining step.

6. The method of claim 1, wherein the classification comprises classifying the cell as a cell that is correlated with a clinical outcome.

7. The method of claim 6, wherein the clinical outcome is the presence or absence of a cancer, metabolic disorder or immune disorder.

8. The method of claim 6, wherein the clinical outcome is the staging or grading of a neoplastic condition.

9. The method of claim 1, wherein the classification further comprises determining a method of treatment.

10. The method of claim 1, wherein the modulator is a cancer cell modulator or hematopoietic cell modulator.

11. The method of claim 1, wherein the modulator is a growth factor, chemokine, cytokine, drug, immune modulator, ion, neurotransmitter, adhesion molecule, hormone, small molecule, inorganic compound, polynucleotide, antibody, natural compound, lectin, lactone, chemotherapeutic agent, biological response modifier, carbohydrate, protease, free radical, complex and undefined biologic composition, cellular secretion, glandular secretion, physiologic fluid, reactive oxygen species, virus, electromagnetic radiation, ultraviolet radiation, infrared radiation, particulate radiation, redox potential, pH modifier, the presence or absences of a nutrient, change in temperature, change in oxygen partial pressure, change in ion concentration or application of oxidative stress.

12. The method of claim 1, wherein the PI3K and/or mTOR pathway modulator is a PI3K and/or mTOR pathway inhibitor is a therapeutic agent.

13. The method of claim 12, wherein the inhibitor is a therapeutic agent.

14. The method of claim 1, wherein the activatable element is a PI3K pathway protein.

15. The method of claim 14, wherein the PI3K pathway protein is PI3K, p110 isoforms, PDK-1, Akt isoforms, PRAS40, Mdm2, TSC2, GSK3β

, BAD, FOXO transcription factors, NFkB, mTOR, p70S6 kinase, Ribosomal S6, 4EBP1, Paxillin, PKCα

, PKCβ

, SGK, TSC1, Rictor or Raptor.

16. The method of claim 1, further comprising analyzing expression level of the PI3K pathway protein.

17. The method of claim 1, wherein the cell is from a patient sample.

18. The method of claim 17, further comprising determining a clinical outcome based on the correlation of the activity of the PI3K regulatory protein with the activity of the PI3K pathway component.

19. The method of claim 18, further comprising determining a method of treatment of the patient based on the correlation of the activity of the PI3K regulatory protein with the activity of the PI3K pathway component.

20. A method of determining the presence or absence of a condition in an individual comprising:

subjecting a cell from the individual to a PI3k and/or mTOR pathway inhibitor;

determining the activation level of an activatable element in the cell; and

determining the presence or absence of the condition based on the activation level.

21. A method of correlating and/or classifying an activatable state of a cancer cell with a clinical outcome in an individual comprising:

subjecting the cancer cell from the individual to a PI3k and/or mTOR pathway modulator;

determining the activation level of an activatable element; and

identifying a pattern of the activation level of the activatable element to determine the presence or absence of an alteration in signaling, wherein the presence of the alteration is indicative of a clinical outcome.

22. A method of analyzing the effect of a compound comprising:

contacting a cell of interest with a compound of interest and analyzing activity of a PI3K and/or mTOR pathway protein in said cell.

23. The method of claim 22, further comprising distinguishing whether the compound is specific for effecting the PI3K pathway, mTOR pathway or modulates both the PI3K and mTOR pathways.