Provided are methods, compositions, kits, and systems for determining the risk that a subject who does not have dysplasia will develop dysplasia and/or esophageal cancer.

The present invention includes compositions and methods for the treatment of cancer comprising an antineoplastic drug and an inhibitor of chromosome maintenance region 1 (CRM1) protein expression or activity, wherein the inhibitor of CRM1 enhances the anti-neoplastic effect of the antineoplastic drug.

The invention relates to an anti-human p53 antibody suitable for specifically binding a linear epitope which is exposed only in a conformationally altered isoform of the characteristic p53 protein of patients with Alzheimer's disease or prone to develop Alzheimer's disease or cognitive impairment during ageing. Methods and diagnostic and prognostic kits are also described.

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.

p53-upregulated modulator of apoptosis (PUMA) is a biomarker associated with islet cell health. If PUMA is low, islet cells are typically healthy. If PUMA is high, islet cells are typically unhealthy or dying. PUMA may be measured by either measuring its nucleic or amino acid. PUMA mRNA may be induced by TNF- stimulation in a time- and dose-dependent manner and cell apoptosis is induced through a mitochondrial pathway. TNF- significantly inhibited glucose-induced preproinsulin precursor mRNA synthesis. Such cell stress signaling in human islets indicates overall state of islet health and, ultimately, the risk of onset and/or degree of severity of both type 1 and type 2 diabetes mellitus.

Described herein are methods of evaluating metastatic potential of a cancer based on the phosphorylation state and/or intracellular localization of iASPP. Therapeutic regimens designed based on the results of the diagnostic methods are also provided.

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 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.

The present application discloses a method to predict responsiveness of a patient, with cancer, to treatment with an MDM2 antagonist of formulae I, II and III as disclosed herein, said method comprising a multivariate analysis comprising detecting relative amounts of certain MDM2 protein expressing cells and, optionally additional co-variates selected from a gene signature as disclosed herein, p53 mutation status, the patient's age and ECOG score at baseline as a biomarker for predicting said patient's response to treatment.

Provided herein are methods and compositions for inhibiting epithelial to mesenchymal transition of a cell.