Disclosed herein are compositions and methods for inhibiting collagen production mediated by the Fused in Sarcoma (FUS) ribonucleoprotein. As disclosed herein, the C terminal domain of FUS contains an uncommon nuclear localization sequence (NLS) motif called PY-NLS that binds the nuclear import receptor transportin. Phosphorylation of FUS leads to its association with transportin and nuclear translocation with consequent increased in collagen production. Therefore, disclosed herein is an isolated peptide having a transportin-binding moiety, which inhibits FUS from binding transportin, linked to a membrane translocating motif. These compositions and methods can be used to inhibit FUS-mediated collagen production, and treat fibrotic disease involving FUS-mediated collagen accumulation in kidneys and other organs displaying fibrotic diseases.

A pharmaceutical composition includes a synthetic peptide consisting of about 10 to about 50 amino acids and having an amino acid sequence substantially homologous to consecutive amino acids of a portion of the cytoplasmic doman of at least one of .sub.v.sub.3 integrin or VEGFR2 that includes a tyrosine residue, the amino acid sequence of the peptide including a phosphorylated tyrosine residue or a -carboxyglutamic acid residue that is substituted for a corresponding tyrosine residue of the portion of the cytoplasmic domain of .sub.v.sub.3 integrin or VEGFR2.

A pharmaceutical composition includes a synthetic peptide consisting of about 10 to about 50 amino acids and having an amino acid sequence substantially homologous to consecutive amino acids of a portion of the cytoplasmic domain of at least one of .sub.v.sub.3 integrin or VEGFR2 that includes a tyrosine residue, the amino acid sequence of the peptide including a phosphorylated tyrosine residue or a -carboxyglutamic acid residue that is substituted for a corresponding tyrosine residue of the portion of the cytoplasmic domain of .sub.v.sub.3 integrin or VEGFR2.

Provided herein are compounds that inhibit a binding interaction between a integrin and a G protein subunit, as well as compositions, e.g., pharmaceutical compositions, comprising the same, and related kits. In some embodiments, the compound is an antibody or antibody analog, and, in other embodiments, the compound is a peptide or peptide analog. Also provided are methods of using the compounds, including methods of treating or preventing a medical condition, such as stroke, heart attack, cancer, or inflammation.

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.

The present invention relates to the field of biotechnology, specifically to an isolated alternative intracellular signalling domain of a chimeric antigen receptor (CAR) and to a chimeric antigen receptor (CAR) comprising, said signalling domain. The invention also relates to a nucleic acid coding an alternative intracellular signalling domain of a chimeric antigen receptor, and to a nucleic acid coding a chimeric antigen receptor with the above-mentioned signalling domain, to an expression vector, to a delivery vector, and also a genetically modified cell which comprises the above-mentioned chimeric antigen receptor, and to a method for producing said cell.

Provided are methods for determining whether a glioblastoma (GBM) tumor or GBM cancer cell will be sensitive to a treatment targeting the integrin avb3 (v3) 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 (v3) pathway, wherein the sensitivity is determined by methods as provided herein.