Abstract: Provided are methods of treating a KRAS mutant cancer in an individual. In certain embodiments, the methods include administering to an individual identified as having a KRAS mutant cancer a therapeutically effective amount of an agent that inhibits cardiotrophin-like cytokine factor 1 (CLCF1)-ciliary neurotrophic factor receptor (CNTFR) signaling. According to some embodiments, the KRAS mutant cancer is a KRAS mutant lung cancer, such as a KRAS mutant non-small cell lung cancer (NSCLC), e.g., a KRAS mutant lung adenocarcinoma (LUAD). Also provided are kits that find use, e.g., in practicing the methods of the present disclosure.

Abstract: Provided are ciliary neurotrophic factor receptor (CNTFR) ligands. In certain aspects, a CNTFR ligand of the present disclosure exhibits increased affinity for CNTFR relative to the corresponding wild-type CNTFR ligand. In certain aspects, a CNTFR ligand of the present disclosure results in reduced binding affinity of glycoprotein 130 (gp130), leukemia inhibitory factor receptor (LIFR), or both, for a complex including the CNTFR ligand and CNTFR, relative to the binding affinity for a complex including the corresponding wild-type CNTFR ligand and CNTFR. In certain aspects, a CNTFR ligand of the present disclosure has both of the aforementioned properties. Also provided are pharmaceutical compositions including the CNTFR ligands, as well as methods of using the CNTFR ligands.

Abstract: Provided are agents that specifically bind a ligand of ciliary neurotrophic factor receptor (CNTFR). In certain aspects, an agent of the present disclosure is a soluble CNTFR polypeptide. The soluble CNTFR polypeptide may have an altered (e.g., reduced) binding affinity for one or more ligand-CNTFR complex subunits, an altered (e.g., increased) binding affinity for one or more CNTFR ligands, or any combination thereof. Compositions that include the agents of the present disclosure are also provided, as are methods of using the agents (e.g., for treating a cell proliferative disorder) and methods of identifying an individual as having a cell proliferative disorder associated with CNTFR signaling.

Abstract: Provided are agents that specifically bind a ligand of ciliary neurotrophic factor receptor (CNTFR). In certain aspects, an agent of the present disclosure is a soluble CNTFR polypeptide. The soluble CNTFR polypeptide may have an altered (e.g., reduced) binding affinity for one or more ligand-CNTFR complex subunits, an altered (e.g., increased) binding affinity for one or more CNTFR ligands, or any combination thereof. Compositions that include the agents of the present disclosure are also provided, as are methods of using the agents (e.g., for treating a cell proliferative disorder) and methods of identifying an individual as having a cell proliferative disorder associated with CNTFR signaling.

Abstract: Provided are ciliary neurotrophic factor receptor (CNTFR) ligands. In certain aspects, a CNTFR ligand of the present disclosure exhibits increased affinity for CNTFR relative to the corresponding wild-type CNTFR ligand. In certain aspects, a CNTFR ligand of the present disclosure results in reduced binding affinity of glycoprotein 130 (gp130), leukemia inhibitory factor receptor (LIFR), or both, for a complex including the CNTFR ligand and CNTFR, relative to the binding affinity for a complex including the corresponding wild-type CNTFR ligand and CNTFR. In certain aspects, a CNTFR ligand of the present disclosure has both of the aforementioned properties. Also provided are pharmaceutical compositions including the CNTFR ligands, as well as methods of using the CNTFR ligands.

Abstract: Provided are agents that specifically bind a ligand of ciliary neurotrophic factor receptor (CNTFR). In certain aspects, an agent of the present disclosure is a soluble CNTFR polypeptide. The soluble CNTFR polypeptide may have an altered (e.g., reduced) binding affinity for one or more ligand-CNTFR complex subunits, an altered (e.g., increased) binding affinity for one or more CNTFR ligands, or any combination thereof. Compositions that include the agents of the present disclosure are also provided, as are methods of using the agents (e.g., for treating a cell proliferative disorder) and methods of identifying an individual as having a cell proliferative disorder associated with CNTFR signaling.

Abstract: Provided are ciliary neurotrophic factor receptor (CNTFR) ligands. In certain aspects, a CNTFR ligand of the present disclosure exhibits increased affinity for CNTFR relative to the corresponding wild-type CNTFR ligand. In certain aspects, a CNTFR ligand of the present disclosure results in reduced binding affinity of glycoprotein 130 (gp130), leukemia inhibitory factor receptor (LIFR), or both, for a complex including the CNTFR ligand and CNTFR, relative to the binding affinity for a complex including the corresponding wild-type CNTFR ligand and CNTFR. In certain aspects, a CNTFR ligand of the present disclosure has both of the aforementioned properties. Also provided are pharmaceutical compositions including the CNTFR ligands, as well as methods of using the CNTFR ligands.

Abstract: The invention provides neuregulin antagonists and methods of using the neuregulin antagonists in delaying the time to tumor recurrence or preventing resistance of cancer cells to treatment with a therapeutic agent.

Abstract: The invention provides neuregulin antagonists and methods of using the neuregulin antagonists in delaying the time to tumor recurrence or preventing resistance of cancer cells to treatment with a therapeutic agent.