A method of characterizing the protein O-GlcNAcylation site-specificity of an antibody. A method of detecting or quantifying the expression of site-specific O-GlcNAcylated proteins expressed in cells and biological samples. A method of diagnosing cancer in a host based on the cellular expression of site-specific O-GlcNAcylated proteins. A method of screening anti-cancer compounds according to their ability to increase a level O-GlcNAcylation of oncogene or tumor suppressor proteins. Methods of treating cancer in an animal host by administering compounds that increase a level of O-GlcNAcylated c-myc or p53 in cancer cells. A method of distinguishing subclasses of pancreatic cancer according to the sensitivity of pancreatic cancer cells to an imidazole derivative, and a method of personalized pancreatic cancer treatment delivered according to the sensitivity subclasses.

Disclosed herein are methods for treating subjects with breast cancer, comprising determining a therapeutic regimen for cancer by measuring the level (amount) of proteins of one or more biomarkers. Also disclosed are methods of treating a subject with breast cancer by predicting or assessing a therapeutic outcome for subject.

Heritable mutations in the BRCA1 and BRCA2 and other genes in the DNA double-strand break (DSB) repair pathway increase risk of breast, ovarian and other cancers. In response to DNA breaks, the proteins encoded by these genes bind to each other and are transported into the nucleus to form nuclear foci and initiate homologous recombination. Flow cytometry-based functional variant analyses (FVAs) were developed to determine whether variants in BRCA1 or other DSB repair genes disrupted the binding of BRCA1 to its protein partners, the phosphorylation of p53 or the transport of the BRCA1 complex to the nucleus in response to DNA damage. Each of these assays distinguished high-risk BRCA1 mutations from low-risk BRCA1 controls. Mutations in other DSB repair pathway genes produced molecular phenocopies with these assays. FVA assays may represent an adjunct to sequencing for categorizing VUS or may represent a stand-alone measure for assessing breast cancer risk.

Methods for treating a proliferative disease in hematologic malignancy in a subject having a complex karyotype by administering an effective amount of an immunotherapy which includes a targeting agent for an epitope of CD33. The proliferative disease may be a hematological disease or disorder such as multiple myeloma, acute myeloid leukemia, myelodysplastic syndrome, and myeloproliferative neoplasm. The effective amount of the anti-CD33 targeting agent may be an amount sufficient to induce myeloconditioning or an amount to induce myeloablation. The methods may further include transplanting allogeneic stem cells to the patient after administration of the anti-CD33 targeting agent.

Heritable mutations in the BRCA1 and BRCA2 and other genes in the DNA double-strand break (DSB) repair pathway increase risk of breast, ovarian and other cancers. In response to DNA breaks, the proteins encoded by these genes bind to each other and are transported into the nucleus to form nuclear foci and initiate homologous recombination. Flow cytometry-based functional variant analyses (FVAs) were developed to determine whether variants in BRCA1 or other DSB repair genes disrupted the binding of BRCA1 to its protein partners, the phosphorylation of p53 or the transport of the BRCA1complex to the nucleus in response to DNA damage. Each of these assays distinguished high-risk BRCA1 mutations from low-risk BRCA1 controls. Mutations in other DSB repair pathway genes produced molecular phenocopies with these assays. FVA assays may represent an adjunct to sequencing for categorizing VUS or may represent a stand-alone measure for assessing breast cancer risk.

Described herein are methods of treating cancer using one or more PRMT5 inhibitors, for example using one or more compounds of Formulae (1-5) or (A-F), pharmaceutically acceptable salts thereof, and/or pharmaceutical compositions thereof. Described herein are methods of treating cancer using one or more PRMT5 inhibitors, for example using one or more compounds of Formulae (1-5) or (A-F), pharmaceutically acceptable salts thereof, and/or pharmaceutical compositions thereof.

Provided herein are methods of treating a patient having a cancer that exhibits (i) a hemizygous loss of the TP53 gene; (ii) a hemizygous loss of the POLR2A gene; and/or (iii) a decreased level of expression of a POLR2A gene product relative to a reference (i.e., control) expression level. The methods comprise administering a therapeutically effective amount of a POLR2A inhibitor (e.g., a nucleic acid that inhibits the expression of a POLR2A protein, an amatoxin, alpha-amanitin, or alpha-amanitin conjugated to a cell targeting moiety, such as an EpCAM antibody) to a patient having or determined to have (i) a hemizygous loss of the TP53 gene; (ii) a hemizygous loss of the POLR2A gene; and/or (iii) a decreased level of expression of a POLR2A gene product relative to a reference (i.e., control) level.

Provided herein are methods of treating a patient having a cancer that exhibits (i) a hemizygous loss of the TP53 gene; (ii) a hemizygous loss of the POLR2A gene; and/or (iii) a decreased level of expression of a POLR2A gene product relative to a reference (i.e., control) expression level. The methods comprise administering a therapeutically effective amount of a POLR2A inhibitor (e.g., a nucleic acid that inhibits the expression of a POLR2A protein, an amatoxin, alpha-amanitin, or alpha-amanitin conjugated to a cell targeting moiety, such as an EpCAM antibody) to a patient having or determined to have (i) a hemizygous loss of the TP53 gene; (ii) a hemizygous loss of the POLR2A gene; and/or (iii) a decreased level of expression of a POLR2A gene product relative to a reference (i.e., control) level.

The present invention relates to a method for maintaining the increased intracellular p53 level, induced by a platinum-based anticancer drug, and an application thereof and, more specifically, to a method for maintaining the increased intracellular p53 level in cells by administering a platinum-based anticancer drug and siRNA to ubiquitin ligase for p53 to a subject in need thereof in combination and sequentially, and a composition for promoting cancer cell apoptosis using the same.

According to the method of the present invention, the increased intracellular p53 expression level can be maintained for a long period of time in spite of the treatment with a low-concentration platinum-based anticancer drug, thereby effectively inducing the apoptosis of cancer cells and minimizing the drug side effect caused by the administration of the platinum-based anticancer drug, and thus the present invention can be favorably used in the prevention of cancer or the development of cancer medicines.

An aspect of the invention provides a method of selectively necrosing cells, comprising: providing a plurality cells, including at least one cancer cell and at least one non-cancerous cell; and administering to the cells a compound, including an HDM-2 targeting component and a cytotoxic component attached to the HDM-2 targeting component, wherein said compound comprises a membrane-active form.