Abstract: This application provides methods of inhibiting an inflammation- or hypoxia-induced death of a cell involving inhibiting an RNF213 signaling pathway. The application further provides methods of preventing or treating various diseases and disorders in a subject involving administering to the subject an inhibitor of expression of RNF213 protein or an inhibitor of one or more functions of the RNF213 protein. The application still further provides methods for enhancing the effectiveness of a cancer treatment in a subject where the cancer involves a hypoxic tumor microenvironment involving co-administering the cancer treatment with an inhibitor or activator of different functions of the RNF213 protein. The application also provides methods of eliminating drug-resistant tumor cells by co-administering an inhibitor of the expression of RNF213 protein or by inhibiting or activating specific functions of the RNF213 protein.

Abstract: Provided are compositions and methods that include binding partners that bind with specificity to target sites on proteins or peptides that comprise a covalently attached molecule. The binding partners are provided as antibodies and antibody derivatives that specifically bind to proteins and peptides that have been covalently modified by attachment of a molecule, such as a drug. The binding partners can bind with specificity to covalently modified peptides when presented in the context of a major histocompatibility complex (MHC). Uses of the compositions and methods for prophylaxis or therapy of disorders are also provided.

Abstract: Provided are methods for treatment of cancer by administering to an individual who has a cancer that includes cancer cells that have an LKBI mutation an anti-CD38 agent, an inhibitor of EP300, or a combination thereof. Methods are also provided for treating an individual who has a cancer that includes cancer cells that do not have an LKBI mutation a Salt-Inducible Kinase (SIK) inhibitor and an anti-CD38 agent. The SIK inhibitors sensitizes the cancer cells that do not have the LKBI mutation to the anti-CD38 agent.

Abstract: Provided are compositions and methods that include binding partners that bind with specificity to target sites on proteins or peptides that comprise a covalently attached molecule. The binding partners are provided as antibodies and antibody derivatives that specifically bind to proteins and peptides that have been covalently modified by attachment of a molecule, such as a drug. The binding partners can bind with specificity to covalently modified peptides when presented in the context of a major histocompatibility complex (MHC). Uses of the compositions and methods for prophylaxis or therapy of disorders are also provided.

Abstract: This invention relates to the purification, cloning and characterization of a novel gene, Gab2. In response to extracellular stimuli (e.g., cyokines, growth factors, hormones and antigens), Gab2 binds several signal relay molecules, including the protein-tyrosine phosphatase SHP-2 and phosphatidylinositol-3-OH kinase (PI-3K), which results in the initiation of multiple signaling cascades. Gab2 nucleic acid molecules, peptides, vectors, host cells, probes, antibodies, knockout and transgenic animals are provided. The invention also relates to methods of diagnosis, prevention and treatment of Gab2-mediated conditions such as allergic responses, neoplastic disorders and immune disorders. The invention further relates to diagnostic kits for disorders associated with altered Gab2 expression.

Abstract: The invention features methods and compositions including an mTOR inhibitor and a tyrosine kinase inhibitor for reducing the proliferation of and enhancing the apoptosis of neoplastic cells. The addition of an MEK inhibitor to this combination further enhances the effectiveness of this therapeutic method.