The invention described herein provides biological markers for the diagnosis, prognosis, and monitoring of prostate cancer.

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 eIF2 axis of the UPR adaptive response. Agents that disrupt PERK-eIF2 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.

The present application provides an agent comprising or consisting of a binding moiety with specificity for a kallikrein protein (for example, PSA or hK2) for use in the treatment of prostate cancer, and a method for the treatment of prostate cancer in a patient, the method comprising the step of administering a therapeutically effective amount of an agent comprising or consisting of a binding moiety with specificity for a kallikrein protein to the patient.

A pro-moiety and a composition comprising a pro-moiety for use in a therapeutically or diagnostically effective amount in a method for detecting and/or treating prostate cancer in a subject is disclosed. The pro-moiety comprises a first peptide, and a second peptide that is linked to the first peptide, wherein the peptide comprises a sequence that is configured near a first terminus for conjugating to a drug to form a prodrug that is rapidly and/or highly selectively cleaved by prostate-specific antigen (PSA), and configured at a second terminus to bind with high selectivity to the active site of PSA, and the second peptide comprises a sequence having a negative charge to slow uptake of the prodrug by cells, and wherein the second peptide is cleaved from the first peptide upon proteolysis by PSA to produce a conjugate of the first peptide and the drug that is suitable for uptake by target cells.

Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

An assay system and method for generating quantitative data for a subject and a method for treating prostate cancer in a subject by determining an expression level of a biomarker panel in a sample obtained from the subject, the biomarker panel including the genes CDC45, CENPI, CLSPN, ERCC6L, EXO1, NCAPG, BUB1B, CDK1, NUSAP1, RAD51, and RRM2 and optionally E2F7 and/or GSG2, wherein the expression level is obtained by measuring expression of the biomarker panel in the sample, and wherein the subject has a cancer, or is suspected of having a cancer. The cancer may be, for example, prostate cancer, brain cancer, lung cancer, breast cancer, bladder cancer, or ovarian cancer.

A method and apparatus for the quantitative determination of an individual's risk for sudden cardiac death (SCD) is described. Risk determination is accomplished and may have a sensitivity and specificity of greater than 95%, by generating linear and nonlinear mathematical digital ECG-constructed models from digital ECG-type data of an individual's digital ECG, determining stability/instability of digital ECG-constructed control model systems corresponding to the digital ECG-constructed models by a plurality of techniques and transforming stability/instability values obtained by the determining stability/instability into a quantitative value reflecting an individual's risk for SCD.

Disclosed are assays, reagents, and methods for ultrasensitive detection of target molecules. The assay comprises fusion proteins including binding moieties, such as antibodies, nanobodies (VHH/VNAR), or aptamers, linked to nonfunctional fragments of a protein. In the presence of a target molecule, the binding moieties recognize distinct target regions and bring the protein fragments into close proximity, reconstituting a functional protein that generates a detectable signal. Linkers connecting the fusion components may be flexible peptides or polypeptides that spontaneously form dimers, trimers, or tetramers, thereby providing multivalent fusion proteins with enhanced sensitivity. The reconstituted protein may produce luminescent, fluorescent, colorimetric, or spectroscopic signals detectable by microplate readers, handheld luminometers, or lateral flow devices. The invention encompasses solid-phase, homogeneous, and lateral flow assay formats for detecting viruses, bacteria, proteins, peptides, or small molecules, including GLRaV-3, SARS-CoV-2, PSA, and E. coli. The disclosed assays exhibit improved specificity, reduced background, and enhanced signal-to-noise ratios.

The invention relates to non-invasive detection of prostate cancer on the basis of altered glycosylation patterns, and to biomarkers for use in the detection and to kits including reagents for determining levels of the biomarkers in biological samples.

The invention relates to non-invasive detection of prostate cancer on the basis of altered glycosylation patterns, and to biomarkers for use in the detection and to kits including reagents for determining levels of the biomarkers in biological samples.