The present invention relates to an in vitro assay for measuring phosphorylated tau in a sample, said assay comprises the use of 2 antibodies i) a capture antibody specific for pS396 on tau and ii) a detection antibody binding tau on a different epitope that the capture antibody.

The present invention relates to a method for diagnosis of cancer and for monitoring the progression of cancer and/or the therapeutic efficacy of an anticancer treatment in a sample of a subject by detecting oncogenic and cancer related proteins in microvesicles, and to the use of an agent blocking exchange of microvesicles for treating cancer.

Noninvasive methods of determining breast cancer subtype in a subject are provided that employ newly identified biomarkers. Said methods comprise isolating a population of extracellular vehicles in a biofluid sample of a subject and detecting differential expression in one or more proteins or peptides therein. Such differential expression is compared to one or more expression profiles within a panel of biomarkers, with each expression profile in the panel associated with a subtype of breast cancer. Also provided are kits for detecting a subtype of breast cancer and/or identifying the recurrence thereof, each comprising an antibody, aptamer, or other detection means against the aforesaid biomarkers. Methods for monitoring treatment efficacy in a subject experiencing breast cancer using the same platforms are also provided.

Method of detecting phosphorylation at Threonine 166 of a Rubicon protein to identify a subject having a disease associated with Leucine-rich repeat kinase 2 (LRRK2) such as Parkinson's disease and compounds and methods for treating the same.

Disclosed herein are methods treating a subject suffering from peritoneal carcinomatosis with a PAI-1 inhibitor, wherein the method comprises determining the concentration of “plasminogen activator inhibitor 1” (PAI-1) and determining the level of phosphorylation of “signal transducer and activator of transcript 3” (STAT3) in a sample obtained from the subject. Also disclosed herein are methods of detecting or determining susceptibility of a subject suffering from peritoneal carcinomatosis to treatment with a PAI-1 inhibitor.

The inventors have found that the interaction between HP1 and INCENP can serve as an indicator for chromosome instability and established a method for evaluating chromosome instability of cancer cells. The evaluation system can be used for screening of anticancer agent with a new-concept of targeting chromosome instability of cancer cells. The inventors further prepared an antibody for specifically recognizing phosphorylation of serine at position 92 of HP1α, by which the action of Aurora B can be evaluated. The interaction between HP1 and INCENP can be readily evaluated by the antibody.

In cancers such as prostate cancer, the combination of PTEN loss and activation of Myc activates an adaptive stress response that enables tumor cells to escape the stress of massively upregulated protein synthesis. This pro-survival response is mediated by the PERK-phosphorylated eIF2α axis of the UPR adaptive response. Agents that disrupt PERK-eIF2α pathways disrupt the adaptive response and lead to cancer cell death from uncontrolled growth. For example, ISRIB and derivatives may be employed as therapeutic agents to disrupt PERK-mediated adaptive mechanisms. Additionally PTEN loss and activation of Myc provides a diagnostic marker that enables better prognosis and the selection of amenable treatments.

Methods for the large scale identification of post-translational modification states of proteins and enzyme activities for carrying out post-translational modification reactions involve the analysis of functional extracts from fresh and frozen samples using protein arrays. The methods and kits of the present invention can be used to analyze and characterize compounds for their effects on post-translational modifications and their pathways. The methods and kits can also be used to diagnose and characterize a wide variety of diseases and medical conditions, including cancer, neurodegenerative diseases, immune diseases, infectious diseases, genetic diseases, metabolic conditions, and drug effects using cells or body fluids of a patient.

The increased efficacy and reduced unwanted side effects of drugs can be insured by treating only responsive patients. In an embodiment of the invention, signaling pathways that a particular drug interferes with, are derive together with predictive biomarkers and dynamic biomarker that can read the activity of these pathways before and after drug treatment in order to select a responder patient population. In an alternative embodiment of the invention, certain core pathways that the drug does not interfere with and that are known to be causally involved in a particular disease(s) can be identified, and derive the biomarkers for those to be able to exclude these patients that suffer from a disease in which those drug non effected pathways are involved from being treated with the specific drug in question.

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.