Abstract: Provided are compositions and methods for treating or ameliorating a cancer by targeting cell surface-expressed ?v?3 (avb3) polypeptides in Cancer Stem Cells (CSCs) to kill the CSCs, thus treating ameliorating or slowing the development of cancers caused or initiated by or sustained by cancer or tumor cells, or Cancer Stem Cells (CSCs), expressing ?v?3 polypeptides on their cell surfaces. Provided are compositions and methods for targeting and killing ?v?3-positive Cancer Stem Cells (CSCs) and treating drug resistant cancers. In alternative embodiments, compositions and methods as provided herein use an antibody that can specifically bind to human ?v?3 that also comprises an Fc portion that can mediate antibody-dependent un-mediated cytotoxicity (ADCC) killing of cancer or tumor cells by macrophages; for example, use a humanized antibody to ?v?3 that has been modified to include an engineered Fc portion that specifically binds to human macrophages.

Abstract: Provided are methods for determining whether a glioblastoma (GBM) tumor or GBM cancer cell will be sensitive to a treatment targeting the integrin avb3 (?v?3) pathway, comprising determining whether the GBM tumor or the GBM cancer cell expresses both avb3+ and Glut3+ along with a specific genetic signature associated with Glut3 addiction, where in alternative embodiments a cell is Glut3 addiction if the GBM tumor or the GBM cancer cell has markers consistent with the Classical or the Proneural molecular subtypes of GBM, or, expresses markers consistent with a Glut3-addicted molecular signature, e.g., as listed in FIG. 11 or FIG. 23. Also provided herein are methods of treating glioblastoma (GBM) tumors found to be sensitive to agents targeting or inhibiting the integrin avb3 (?v?3) pathway, wherein the sensitivity is determined by methods as provided herein.

Abstract: The present invention relates to chimeric binding agents and compositions comprising the same. The invention further relates to polynucleotides encoding the chimeric binding agent and vectors and host cells comprising the same. The invention further relates to methods of using the chimeric binding agents to mediate antibody-dependent cellular cytotoxicity of epithelial cancer cells and methods of treating epithelial cell cancers.

Abstract: In alternative embodiments, provided are products of manufacture, such as assays, chimeric nucleic acids and nucleic acid constructs, recombinant cells, and methods, comprising use of beta3-integrin (ITGB3) promoters operatively linked to a reporter, for drug screening, and in particular, screening for agents that inhibit cancer cell survival and metastasis. In alternative embodiments, compositions and methods as provided herein also can be used to identifying novel pathways that lead to acquired resistance, stemness, and anchorage independent growth; and characterizing distinct populations of cancer cells within a tumor microenvironment.

Abstract: In alternative embodiments, provided are compositions and methods for treating or ameliorating an advanced cancer such as a drug resistant or metastatic cancer which express ?v?3 polypeptides on their cell surfaces, or for killing Cancer Stem Cells (CSCs) which express ?v?3 polypeptides on their cell surfaces, by using human or humanized antibodies capable of specifically binding cell surface-expressed ?v?3 (avb3) polypeptides whose Fc region has a selective affinity to human Fc?R1 (CD64), but not to other Fc?Rs, on effector cells such as macrophages, neutrophils, and dendritic cells. By administering these antibodies to an individual in need thereof, these human or humanized antibodies are capable of treating, ameliorating or slowing the development of the advanced cancer or drug resistant cancer, or a cancer caused or initiated by or sustained by an advanced cancer or drug resistant cancer cell, or a Cancer Stem Cell (CSC).

Abstract: Provided are methods for determining whether a glioblastoma (GBM) tumor or GBM cancer cell will be sensitive to a treatment targeting the integrin avb3 (?v?3) pathway, comprising determining whether the GBM tumor or the GBM cancer cell expresses both avb3+ and Glut3+ along with a specific genetic signature associated with Glut3 addiction, where in alternative embodiments a cell is Glut3 addiction if the GBM tumor or the GBM cancer cell has markers consistent with the Classical or the Proneural molecular subtypes of GBM, or, expresses markers consistent with a Glut3-addicted molecular signature, e.g., as listed in FIG. 11 or FIG. 23. Also provided herein are methods of treating glioblastoma (GBM) tumors found to be sensitive to agents targeting or inhibiting the integrin avb3 (?v?3) pathway, wherein the sensitivity is determined by methods as provided herein.

Abstract: Provided are compositions and methods for treating or ameliorating a cancer by targeting cell surface-expressed ALPHA-V BETA-3 polypeptides in Cancer Stem Cells (CSCs) to kill the CSCs, to treat cancers caused or initiated by cancer or tumor 10 cells, or Cancer Stem Cells (CSCs), expressing ALPHA-V BETA-3 polypeptides on their cell surfaces. Provided are compositions and methods for targeting and killing ALPHA-V BETA-3-positive Cancer Stem Cells (CSCs) and treating drug resistant cancers. In alternative embodiments, compositions and methods as provided herein use an antibody that can specifically bind to human ALPHA-V BETA-3 that also comprises an Fc portion that can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) killing of cancer cells by macrophages; for example, use a humanized antibody to ALPHA-V BETA-3 that has been modified to include an engineered Fc portion that specifically binds to human macrophages.

Abstract: Provided are methods for making highly dedifferentiated and stem-like human cells from human umbilical vein endothelial cells (HUVECs) ectopically expressing integrin ?3. Also provided are methods for making ectoderm, mesoderm, and endoderm cells from HUVECs ectopically expressing integrin ?3. Also provided are methods for making neural cells, or cells having neuronal-like morphology, from HUVECs ectopically expressing integrin ?3. Provided are methods for making cardiomyocytes, or cells having cardiomyocyte-like morphology, from HUVECs ectopically expressing integrin ?3. Provided are methods for the production of pluripotent stem cells comprising expressing integrin ?3 in primary human endothelial cells. In alternative embodiments, provided are methods for inducing ?v?3 clustering, and to accelerate or facilitate angiogenesis, tissue remodeling or repair, or wound healing, for example, to accelerate healing after an infarction.

Abstract: In alternative embodiments, provided are products of manufacture, such as assays, chimeric nucleic acids and nucleic acid constructs, recombinant cells, and methods, comprising use of beta3-integrin (ITGB3) promoters operatively linked to a reporter, for drug screening, and in particular, screening for agents that inhibit cancer cell survival and metastasis. In alternative embodiments, compositions and methods as provided herein also can be used to identifying novel pathways that lead to acquired resistance, stemness, and anchorage independent growth; and characterizing distinct populations of cancer cells within a tumor microenvironment.

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.

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.

Abstract: In alternative embodiments, provided are products of manufacture, such as assays, chimeric nucleic acids and nucleic acid constructs, recombinant cells, and methods, comprising use of beta3-integrin (ITGB3) promoters operatively linked to a reporter, for drug screening, and in particular, screening for agents that inhibit cancer cell survival and metastasis. In alternative embodiments, compositions and methods as provided herein also can be used to identifying novel pathways that lead to acquired resistance, stemness, and anchorage independent growth; and characterizing distinct populations of cancer cells within a tumor microenvironment.

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.

Abstract: In alternative embodiments, the invention provides compositions and methods comprising use of microRNAs and microRNA inhibitors to modulate blood vessel growth (angiogenesis), e.g., act as anti-angiogenic agents, and modulate cell and tumor microenvironment patterning, cancer cell and tumor growth and malignant disease (metastasis). In alternative embodiments, the invention provides compositions and methods that can sensitize blood vessels, e.g., tumor blood vessels, to radiation and agents and chemotherapies that cause DNA damage.

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.

Abstract: In alternative embodiments, the invention provides compositions and methods for identifying individuals that would be responsive to a treatment comprising (including) blocking activation of integrin polypeptide alphav-beta3 (or ?v-?3), or blocking the interaction of a ligand with integrin polypeptide alphav-beta3 (or ?v-?3). The invention provides compositions and methods for determining the effectiveness of such a treatment and can contribute to a prognosis for the patient.

Abstract: In alternative embodiments, the invention provides compositions and methods comprising use of microRNAs and microRNA inhibitors to modulate blood vessel growth (angiogenesis), e.g., act as anti-angiogenic agents, and modulate cell and tumor microenvironment patterning, cancer cell and tumor growth and malignant disease (metastasis). In alternative embodiments, the invention provides compositions and methods that can sensitize blood vessels, e.g., tumor blood vessels, to radiation and agents and chemotherapies that cause DNA damage.

Abstract: In alternative embodiments, the invention provides methods for regulating or modulating RAF kinases. In alternative embodiments, the invention provides methods for ameliorating, preventing and/or treating diseases, infections and/or conditions having unwanted, pathological or aberrant cell proliferation, or that are responsive to inhibition or arrest of cell growth, by administration of an allosteric RAF inhibitor and/or any agent which prevents localization of RAF to mitotic spindles or mid-bodies.

Abstract: The invention provides nanostructures or products of manufacture for use as ex vivo or in vivo composition (e.g., a drug, or a therapeutic, diagnostic or imaging reagent) delivery vehicles. In one aspect, the invention provides nanoparticles comprising several compartments which in unison function as a composite nanostructure. In one embodiment, the nanoparticles of the invention comprise a combination of polymer core/lipid bilayer interface which incorporate covalently attached lipid-vascular targeting ligands. These composite nanoparticles can deliver highly effective and selective payloads for diagnostic, prophylactic or therapeutic applications.

Abstract: The invention provides compositions, e.g., small molecules, that disrupt the activity of protein kinases, including constitutively activated protein kinases, such as kinases constitutively activated through mutations, and kinases in their native inactivated state, and methods for making and using them. In one aspect, compositions of the invention bind a protein kinase in its inactive conformation involving the conserved asparagine-phenylalanine-glycine residue motif, or “Asp-Phe-Gly” or “DFG” motif, of the activation loop in the allosteric binding site. The small molecule protein kinase inhibitors of the invention comprise or are derivatives or analogs of oxadiazoles, thiadiazoles, oxazoles, thiazoles, arylamides, quinolones, pyrazoles, pyrazolones, imides, pyrolles, imidazoles and/or triazoles.