Compositions and methods for the treatment of malignancy are disclosed.

Disclosures herein are directed to methods and compositions for the detection of a panel of proteins as markers for ASD. Based on the results achieved from the methods disclosed herein, ASD can be diagnosed and suitable treatments for ASD may be designed and administered to the subject.

The present invention provides a method for providing information for diagnosis of metastasis of radiotherapy-treated lung cancer, the method comprising the steps of: (a) measuring an expression level of receptor-interacting protein kinase 1 (RIP1) in a sample from a lung cancer patient who has undergone radiotherapy; (b) measuring an expression level of RIP1 in a normal control sample; and (c) comparing the expression levels of step (a) and step (b).

The present invention relates to a method of using Focal Adhesion Kinase (FAX) as a predictive marker to identify patients with early-stage colorectal cancer (CRC) at risk for recurrence. In particular, the present invention is a prognostic assay using FAK protein expression to predict those CRC patients with Stage I disease who may recur. The present invention will allow for quantitative measurement of the expression of FAK in tumor tissue of patients with early-stage CRC. As patients with stage I CRC are typically only treated with surgical resection, the present invention will uniquely facilitate the identification of those early-stage CRC patients who are at risk of recurrence and who may benefit from adjuvant therapy after resection of the primary cancer. This invention is not limited to patients with CRC and may be utilized for any condition that is caused by or causes FAK overexpression or dysfunction.

The present invention relates to binding agents of human Leucine-rich Repeat Kinase 2 (LRRK2). More particular, allosteric modulators of LRRK2 activity have been identified, for targeting LRRK2 in human cells, while leaving LRRK2 subcellular localisation unaffected. Even more specifically, protein binding agents for allosteric modulation of LRRK2 kinase activity are disclosed, comprising immunoglobulin single variable domains (ISVDs) binding to human LRRK2 with nanomolar affinity. The invention thus reveals means and methods for a novel LRRK2 targeting approach through allosteric modulation of its activity for use in treatment of LRRK2-related pathologies, such as Parkinson's disease, as well as for use in detection of LRRK2 in vitro and in vivo, and for use as a diagnostic.

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 novel antibody or an antigen binding fragment thereof that specifically binds to a human hepatocyte growth factor receptor (c-Met), and a composition for preventing or treating cancer, wherein the antibody shows an excellent cancer cell proliferation inhibitory activity and a remarkably excellent anticancer activity even by a little amount thereof, thus effectively preventing or treating cancer.

A compound represented by the following general formula (I) [the symbol in the formula are as defined in the description], a salt thereof, or the like is a RET inhibitor or RET tyrosine kinase inhibitor that can he used as an agent for the prevention or treatment of disorders including cancers and cancer metastasis having mutations in RET. ##STR00001##

Disclosed herein are serine threonine kinase (AKT) degradation/disruption compounds including an AKT ligand, a degradation/disruption tag, and a linker, and methods of using such compounds in the treatment of AKT-mediated diseases.

The invention relates to method of diagnosis a subject suffering from Adult-onset Still's disease and further to determine the disease course of the subject suffering from Adult-onset Still's disease.