Abstract: Inhibitors of Glycerol 3-Phosphate Acyltransferase (GPAT) are provided; and methods of use in the treatment of cancer; and treatment of conditions relating to metabolic syndrome and hyperlipidemia.

Abstract: Compositions and methods are provided for classification and treatment of MYC-driven cancers, i.e. causally dependent on MYC as a result of, over-expression of MYC, constitutive expression of MYC, chromosomal translocation resulting in overactive MYC, and the like. Specifically, the methods comprising determining the MYC status of the cancer, and in a cancer that is determined to be driven by MYC activation, administering a composition of an effective dose of one or both of activated natural killer (NK) cells and a type 1 interferon.

Abstract: Compositions and methods are provided for alleviating cancer in a mammal.

Abstract: Anti-PD-1/PD-L1 antibody conjugated nanoparticles and methods of treating cancer, including without limitation hepatocellular carcinoma, are provided. The conjugates comprise antibodies, e.g. antibody F(ab) fragments, covalently linked to nanopartides. The antibody conjugated nanoparticles provide high tumor-specific delivery by extending circulation time of the antibodies by increasing their geometry and removing the Fc portion, and minimizing off-target distribution and toxicity. In some embodiments the antibody conjugated nanoparticlesprovide for increased therapeutic efficacy, e.g. in decreased tumor growth, relative to unconjugated antibody, or relative to unconjugated F(ab) fragments of an antibody.

Abstract: Methods are provided for treating a subject having a MYC-driven neoplasia. Aspects of the methods include administering to the subject an amount of an inhibitor of a target gene effective to treat the subject for the MYC-driven neoplasia. Methods are also provided for identifying a MYC-dependent target gene in a MYC-driven neoplasia. Aspects of the method include identifying the MYC-dependent target gene based on a phenotype detected in a first tumor cell line conditionally expressing MYC that is absent or quantitatively different in a second tumor cell line conditionally repressing MYC when the two cell lines are contacted with a CRISPR-based gene silencing agent. Kits and cell lines for practicing the methods of the disclosure are also provided.

Abstract: Methods of inhibiting the proliferation of a cancer cell, and treating cancer in an individual are provided. Aspects of the subject methods include contacting a cancer cell with an azapodophyllotoxin derivative, where the contacting is effective to inhibit tubulin polymerization and monoglycerol metabolism to inhibit proliferation of cancer in the cell. In certain cases, the cancer cell is a renal cancer cell (RCC) or a lymphoma cell. Aspects of the methods also include administering to a subject an effective amount of an azapodophyllotoxin derivative to treat the subject for cancer, where the cancer is selected from renal cancer and lymphoma. Also provided is a method of monitoring tumor regression in an individual, and methods of identifying a cancer suppressing compound.

Abstract: Inhibitors of Glycerol 3-Phosphate Acyltransferase (GPAT) are provided; and methods of use in the treatment of cancer; and treatment of conditions relating to metabolic syndrome, hyperlipidemia, infection and inflammation.

Abstract: Inhibitors of Glycerol 3-Phosphate Acyltransferase (GPAT) are provided; and methods of use in the treatment of cancer; and treatment of conditions relating to metabolic syndrome and hyperlipidemia.

Abstract: Compositions and methods are provided for classification and treatment of MYC-driven cancers, i.e. causally dependent on MYC as a result of, over-expression of MYC, constitutive expression of MYC, chromosomal translocation resulting in overactive MYC, and the like. Specifically, the methods comprising determining the MYC status of the cancer, and in a cancer that is determined to be driven by MYC activation, administering a composition of an effective dose of one or both of activated natural killer (NK) cells and a type 1 interferon.

Abstract: Methods are provided for the detection and treatment of cancers having a KRAS mutation, which KRAS mutation may drive tumorigenesis in the cancer. In some embodiments the KRAS+ cancer is a lung adenocarcinoma.

Abstract: Methods are provided for treating a subject having a MYC-driven neoplasia. Aspects of the methods include administering to the subject an amount of an inhibitor of a target gene effective to treat the subject for the MYC-driven neoplasia. Methods are also provided for identifying a MYC-dependent target gene in a MYC-driven neoplasia. Aspects of the method include identifying the MYC-dependent target gene based on a phenotype detected in a first tumor cell line conditionally expressing MYC that is absent or quantitatively different in a second tumor cell line conditionally repressing MYC when the two cell lines are contacted with a CRISPR-based gene silencing agent. Kits and cell lines for practicing the methods of the disclosure are also provided.

Abstract: Methods are provided for the analysis, including the serial analysis, of very small samples of tissue. The methods utilize a nanofluidic proteomic immunoassay (NIA) to quantify total and low-abundance protein isoforms in a small amount of lysate. NIA detection accurately measure oncoprotein expression and activation in limited clinical specimens, including isoforms that differ in post-translational modifications, such as phosphorylation, and the like. The NIA detection method combines isoelectric protein focusing and antibody detection in a nanofluidic system.

Abstract: A nanoimmunoassay (NIA) is applied to quantify analytes, including without limitation proteins and isoforms of proteins involved in oncogenic or metabolic signaling pathways, in a small amount of lysate from a tissue sample. Samples of interest for NIA include without limitation blood or solid tumor microbiopsy samples, such as fine needle aspirate (FNA) or circulating tumor cells. Samples may be taken at a single timepoint, or may be taken at multiple timepoints. Samples may be as small as 100,000 cells, as small as 5000 cells, as small as 1000 cells, as small as 100 cells, as small as 50 cells, as small as 25 cells or less. The NIA detection method combines size separation of proteins or isoelectric protein focusing and antibody detection in a microfluidic system.

Abstract: Provided are methods of identifying whether a subject having cancer will be responsive to agents that combat immune evasion, such as immune checkpoint inhibitors. Methods of treating a subject having cancer are also provided. Such methods may include those that involve identifying whether the cancer will be responsive to an immune checkpoint inhibitor and/or is an immune-evasive cancer and administering an agent, e.g., an immune checkpoint inhibitor and/or a MYC inhibitor, to the subject to treat the cancer. Also provided are methods of identifying cancer therapeutics that are effective during MYC-regulated immune evasion as well as cancer cell lines and transgenic animals useful in such methods. Kits for use in the described methods are also provided.

Abstract: Methods are provided for the analysis, including the serial analysis, of very small samples of tissue. The methods utilize a nanofluidic proteomic immunoassay (NIA) to quantify total and low-abundance protein isoforms in a small amount of lysate. NIA detection accurately measure oncoprotein expression and activation in limited clinical specimens, including isoforms that differ in post-translational modifications, such as phosphorylation, and the like. The NIA detection method combines isoelectric protein focusing and antibody detection in a nanofluidic system.

Abstract: Provided are MYC-reporters and MYC-reporter expression vectors having MYC-reporter activity. Also provided are cells containing MYC-reporters and/or MYC-reporter expression vectors as well as animals containing such cells and/or genetically modified to contain one or more MYC-reporters and/or expression vectors. Also provided are methods of screening, including methods of screening a candidate agent for MYC repression. The subject methods may, in some instances, employ one or more of the provided MYC-reporters, expression vectors, cells and/or transgenic animals.

Abstract: Methods are provided for the analysis, including the serial analysis, of very small samples of tissue. The methods utilize a nanofluidic proteomic immunoassay (NIA) to quantify total and low-abundance protein isoforms in a small amount of lysate. NIA detection accurately measure oncoprotein expression and activation in limited clinical specimens, including isoforms that differ in post-translational modifications, such as phosphorylation, and the like. The NIA detection method combines isoelectric protein focusing and antibody detection in a nanofluidic system.

Abstract: Expression of MYC alone, in a conditional transgenic mouse model of Twist1- and MYC-induced hepatocellular carcinoma (HCC), resulted in tumors that failed to metastasize, whereas Twist1 co-expression with MYC resulted in tumors associated with extra-hepatic metastases to the lymph nodes, spleen, peritoneum, and lungs. Twist1 also caused a marked increase in circulating tumor cells. Combined inactivation of Twist1 and MYC resulted in sustained regression of both primary and metastatic tumors as shown by gross and microscopic pathology, X-ray computed tomography and bioluminescence imaging, as well as the suppression of circulating tumor cells. Through genomic analysis a 20-gene signature comprising 17 up-regulated genes and 3 down-regulated genes has been identified that is highly predictive of metastasis and overall survival in human patients with HCC.

Abstract: Methods are provided for the analysis, including the serial analysis, of very small samples of tissue. The methods utilize a nanofluidic proteomic immunoassay (NIA) to quantify total and low-abundance protein isoforms in a small amount of lysate. NIA detection accurately measure oncoprotein expression and activation in limited clinical specimens, including isoforms that differ in post-translational modifications, such as phosphorylation, and the like. The NIA detection method combines isoelectric protein focusing and antibody detection in a nanofluidic system.