Compositions and methods for treating cancer and diseases and conditions responsive to cell growth inhibition

Patent metadata

Field	Value
Publication number	US-9632074-B2
Application number	US-201414325288-A
Country	US
Kind code	B2
Filing date	Jul 7, 2014
Priority date	Apr 5, 2012
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

In alternative embodiments, the invention provides compositions and methods for overcoming or diminishing or preventing Growth Factor Inhibitor resistance in a cell, or, a method for increasing the growth-inhibiting effectiveness of a Growth Factor inhibitor on a cell, or, a method for re-sensitizing a cell to a Growth Factor Inhibitor, comprising for example, administration of a combination of a TBK1 inhibitor and an RTK inhibitor. In alternative embodiments, the cell is a tumor cell, a cancer cell or a dysfunctional cell. In alternative embodiments, the invention provides compositions and methods for determining: whether an individual or a patient would benefit from or respond to administration of a Growth Factor Inhibitor, or, which individuals or patients would benefit from a combinatorial approach comprising administration of a combination of: at least one growth factor and at least one compound, composition or formulation used to practice a method of the invention, such as an NFKB inhibitor, such as a lenalidomide or a REVLIMID™, or IKK inhibitor; or an inhibitor of Galectin-3.

First claim

What is claimed is:

1. A method for: overcoming or diminishing a Growth Factor Inhibitor (GFI) resistance in a cell, or sensitizing, increasing sensitivity to or re-sensitizing a tumor that is resistant to a cancer or anti-tumor Growth Factor Inhibitor (GFI) drug, wherein the Growth Factor Inhibitor is an erlotinib, a linsitinib, a lapatinib or a lenalidomide, comprising administering to the cell or an individual in need thereof at least one compound, composition or formulation comprising an inhibitor of Galectin-3; thereby overcoming or diminishing the Growth Factor Inhibitor (GFI) resistance in the cell, or sensitizing, increasing sensitivity or re-sensitizing the tumor that is resistant to the cancer or anti-tumor Growth Factor Inhibitor (GFI) drug.

2. The method of claim 1 , wherein:
(a) the at least one compound, composition or formulation, or combination of compounds, is formulated as a pharmaceutical composition;
(b) the method of (a), wherein the compound, composition or formulation or pharmaceutical composition is administered in vitro, ex vivo or in vivo, or is administered to an individual in need thereof; or
(c) the method of (a) or (b), wherein the at least one compound, composition or formulation is a pharmaceutical composition which is formulated for administration intravenously (IV), parenterally, nasally, topically, orally, or by liposome or targeted or vessel-targeted nanoparticle delivery.

3. The method of claim 1 , wherein the growth factor inhibitor or Growth Factor Inhibitor (GFI) drug comprises an erlotinib or a lapatinib.

4. The method of claim 1 , wherein the Growth Factor Inhibitor or Growth Factor Inhibitor (GFI) drug decreases, slows or blocks new blood vessel growth, neovascularization or angiogenesis; or, wherein the administering of the Growth Factor Inhibitor treats or ameliorates conditions that are responsive to blocking or slowing cell growth, and/or the development of neovascularization or new blood vessels.

5. The method of claim 1 , wherein the at least one compound, composition or formulation, or combination of compounds further comprises at least one growth factor inhibitor or Growth Factor Inhibitor (GFI) drug.

6. A method for: sensitizing, increasing sensitivity to or re-sensitizing a tumor that is resistant to a Receptor Tyrosine Kinase (RTK) inhibitor in an individual in need thereof, wherein the RTK inhibitor is an erlotinib, a lapatinib or a lenalidomide, comprising administering a sufficient amount of at least one compound, composition or formulation to the individual in need thereof, wherein the at least one compound, composition or formulation comprises an inhibitor of Galectin-3.

7. The method of claim 6 , wherein the RTK inhibitor is an erlotinib or a lapatinib.

8. The method of claim 1 , wherein the inhibitor of Galectin-3 comprises a Galectin-3-specific shRNA (sh Gal-3).

9. The method of claim 6 , wherein the inhibitor of Galectin-3 comprises a Galectin-3-specific shRNA (sh Gal-3).

10. The method of claim 6 , wherein:
(a) the at least one compound, composition or formulation, or combination of compounds, is formulated as a pharmaceutical composition;
(b) the method of (a), wherein the compound, composition or formulation or pharmaceutical composition is administered ex vivo or in vivo to the individual in need thereof; or
(c) the method of (a) or (b), wherein the at least one compound, composition or formulation is a pharmaceutical composition which is formulated for administration intravenously (IV), parenterally, nasally, topically, orally, or by liposome or targeted or vessel-targeted nanoparticle delivery.

11. The method of claim 6 , wherein the method reduces, treats or ameliorates the level of disease in a cancer or a carcinoma.

12. The method of claim 11 , wherein the cancer or a carcinoma is a glioblastoma, a neuroma, a neuroblastoma or a colon carcinoma.

13. The method of claim 1 , wherein the method reduces, treats or ameliorates a cancer or carcinoma.

14. The method of claim 13 , wherein the cancer or carcinoma is a glioblastoma, a neuroma, a neuroblastoma, a colon carcinoma.

Assignees

• Univ California

Inventors

• Cheresh David
• Seguin Laetitia
• Anand Sudarshan

Classifications

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/454

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone · CPC title

• A61K38/05

  Dipeptides · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title