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.

A method of diagnosing breast cancer is disclosed. The method comprises lysing extracellular vesicles of a subject to generate a composition comprising components of extracellular vesicles; measuring the amount of MEK1 in the composition; and diagnosing the subject with breast cancer when a level of said MEK1 in said composition is above a predetermined threshold. Kits for breast cancer diagnosis are also disclosed.

The present invention is directed toward novel methods to identify as well as to treat a subject having an inflammatory disease resistant to corticosteroids.

Studies in mouse models of Fragile X and preliminary studies in human youth demonstrate that ERK1/2 is biomarker useful to monitoring the treatment of people diagnosed with ASD. Results reported herein demonstrate that acamprosate has the ability to reduce levels of ERK1/2 activation associated with many of the symptoms of ASD. Accordingly, in addition to its utility as a diagnostic marker for ASD ERK1/2 activation levels can be used to monitor patients treated with acamprosate and to screen potentially therapeutic compounds.

The current disclosure relates to pharmaceutical combinations and compositions useful in the treatment of certain types of cancer. The disclosure also relates to methods for treatment of these types of cancer. In particular, the disclosure relates to the combined use of of an inhibitor of a protein of the MAPK/ERK pathway and an inhibitor of specific kinases in the treatment of a cancer, in particular melanoma, in a patient. In an important embodiment, the cancer is characterized by the absence or reduced expression of MITF.

The present invention found that, for example, inhibiting phosphorylation of a Ser residue in Regnase-1 is effective in treating and/or preventing diseases. The invention also found that, for example, inhibiting the binding of Regnase-1 with at least one factor selected from the group consisting of TBK1, IKKi, Act-1, IKK, and IRAK is effective in treating and/or preventing diseases.

Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-associated disorder or disease and methods of diagnosing a KIT-associated disorder or disease using the antibodies described herein.

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound.

Therapeutic Agents, Pharmaceutical Compositions, and Associated Biomarkers The invention relates to the identification of pharmaceutical compositions, therapeutic agents, peptides, nucleic acids, genetic constructs, vectors, cells, and medicaments, and their use in methods of treatment. For example, the treatment of neuropathological conditions, in particular Alzheimer's disease. Furthermore, provided herein are biomarkers, methods for their use, methods of diagnosis, methods of monitoring disease progression, and methods for monitoring medicament efficacy, in particular for Alzheimer's disease.

Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.