Combination therapy to prevent DCIS formation and progression to breast cancer
A method of treating a ductal carcinoma in situ (DCIS) lesion in a subject in need thereof is disclosed. The method comprises administering to the subject a therapeutically effective amount of a first agent capable of down-regulating activity and/or expression of at least one component participating in a NOTCH pathway, and a second agent capable of down-regulating an activity and/or expression of HER2, thereby treating the DCIS lesion.
1. A method of treating a ductal carcinoma in situ (DCIS) lesion in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a first agent capable of down-regulating activity and/or expression of at least one component participating in a NOTCH pathway, and a second agent capable of down-regulating an activity and/or expression of HER2, wherein said second agent is an antibody, thereby treating the DCIS lesion.
2. The method of claim 1 , further comprising analyzing in a breast sample of said subject an expression of said at least one component participating in a NOTCH pathway, prior to said treating.
3. The method of claim 2 , further comprising analyzing in a breast sample of said subject an expression of HER2 prior to said treating.
4. The method of claim 1 , further comprising analyzing in a breast sample of said subject an expression of HER2 prior to said treating.
5. The method of claim 1 , wherein said antibody comprises Trastuzumab.
6. The method of claim 1 , wherein said at least one component is selected from the group consisting of Hairy and Enhancer of Split 1(HES1), NOTCH 2, NOTCH 3, ADAM17 and Presenilin1.
7. The method of claim 1 , wherein said at least one component is NOTCH3.
8. The method of claim 1 , wherein said first agent is an siRNA molecule.
9. The method of claim 1 , wherein said first agent is a gamma secretase inhibitor, a mitogen-activated protein kinase (MEK) specific inhibitor or a PI3K-AKT inhibitor.
10. The method of claim 9 , wherein said first agent is a gamma secretase inhibitor.
11. A method of treating a ductal carcinoma in situ (DCIS) lesion in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a first agent selected from the group consisting of an antibody, an RNA silencing agent and an antagonist molecule capable of down-regulating activity and/or expression of at least one component participating in a NOTCH pathway selected from the group consisting of a NOTCH receptor, NOTCH ligand, NOTCH receptor intracellular domain (NICD), ADM17, presenilinl, HES, HERP, HEY, RBPSUH, Su(H), Lag-1, c-Myc and Cyclin D1, gamma-secretase, mitogen-activated protein kinase (MEK) and PI3K-AKT, and a second agent selected from the group consisting of an antibody, an RNA silencing agent and a kinase inhibitor molecule capable of down-regulating an activity and/or expression of HER2, thereby treating the DCIS lesion.
12. The method of claim 11 , further comprising analyzing in a breast sample of said subject an expression of said at least one component participating in a NOTCH pathway, prior to said treating.
13. The method of claim 12 , further comprising analyzing in a breast sample of said subject an expression of HER2 prior to said treating.
14. The method of claim 11 , further comprising analyzing in a breast sample of said subject an expression of HER2 prior to said treating.
15. The method of claim 11 , wherein said second agent is an antibody.
16. The method of claim 15 , wherein said antibody comprises Trastuzumab.
17. The method of claim 11 , wherein said second agent is a kinase inhibitor.
18. The method of claim 17 , wherein said kinase inhibitor is lapatinib.
19. The method of claim 11 , wherein said at least one component is selected from the group consisting of Hairy and Enhancer of Split 1 (HES1), NOTCH 2, NOTCH 3, ADAM17 and Presenilin1.
20. The method of claim 11 , wherein said at least one component is NOTCH3.
21. The method of claim 11 , wherein said first agent is an siRNA molecule.
22. The method of claim 11 , wherein said first agent is a gamma secretase inhibitor, a mitogen-activated protein kinase (MEK) specific inhibitor or a PI3K-AKT inhibitor.
23. The method of claim 11 , wherein said first agent is a gamma secretase inhibitor.