Targeting a non-canonical notch signaling pathway for cancer treatment
View Patent ↗Methods and compositions are provided for treating an individual having cancer. Aspects of the methods include administering to the individual an inhibitor of a non-canonical Notch signaling pathway gene in an amount effective to treat the cancer. Also provided are reagents, devices and kits thereof that find use in practicing the subject methods.
1. A method of treating an individual for a brain tumor or a hematological malignancy, the method comprising:
administering to the individual an inhibitor of a member of a non-canonical Notch signaling pathway that includes Notch and a protein that promotes mitochondrial development or function in an amount effective to treat the brain tumor or hematological malignancy.
2. The method according to claim 1 , wherein the protein that promotes mitochondrial development or function is expressed by a gene selected from a mitochondrial quality control gene, a respiratory chain complex gene, mitochondrial fission gene, and the mitochondrial biogenesis gene.
3. The method according to claim 1 , wherein the protein that promotes mitochondrial development or function is selected from PTEN-induced putative kinase 1 (PINK1), RCC-I (respiratory chain complex I) 75 kD subunit (ND-75), Dynamin-related protein 1 (Drp1), and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α).
4. The method according to claim 1 , wherein the method is a method for treating an individual for a brain tumor.
5. The method according to claim 1 , wherein the method is a method for treating an individual for a hematological malignancy.
6. The method according to claim 5 , wherein the hematological malignancy is T-cell acute lymphoblastic leukemia (T-ALL).
7. The method according to claim 4 , wherein the brain tumor is glioblastoma multiforme (GBM).
8. The method according to claim 4 , further comprising determining if the individual has a Notch-associated cancer, and administering the inhibitor based on the determination.
9. The method according to claim 1 , further comprising detecting a reduction of proliferation of the brain tumor cells or hematological malignancy cells, wherein a reduction in the proliferation indicates that the brain tumor or hematological malignancy is treated.
10. The method according to claim 1 , wherein the inhibitor targets Drp1, mTOR or mitochondrial complex I.
11. The method according to claim 10 , wherein the inhibitor is selected from Mdivi-1, Ku-0063794 and rotenone.
12. The method according to claim 11 , wherein the inhibitor is Mdivi-1.
13. The method according to claim 11 , wherein the inhibitor is Ku-0063794.
14. The method according to claim 11 , wherein the inhibitor is rotenone.
15. The method according to claim 1 , wherein the pathway comprises Notch, PINK1, and at least one RCC-I subunit, rapamycin complex 2 (mTORC2), and protein kinase B (AKT).
16. The method according to claim 1 , wherein the pathway comprises Notch and PINK1.
17. The method according to claim 1 , wherein the pathway comprises Notch and at least one RCC-I subunit.
18. The method according to claim 1 , wherein the pathway comprises Notch and mTORC2.
19. The method according to claim 1 , wherein the pathway comprises Notch and AKT.
20. The method according to claim 1 , wherein the inhibitor targets PTEN-induced putative kinase 1 (PINK1).
21. The method according to claim 1 , wherein the inhibitor targets RCC-I (respiratory chain complex I) 75 kD subunit (ND-75).
22. The method according to claim 1 , wherein the inhibitor targets Dynamin-related protein 1 (Drp1).
23. The method according to claim 1 , wherein the inhibitor targets Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α).