The invention refers to a method for diagnosing an individual who is to be subjected to or is being subjected to an anti-tumor necrosis factor alpha (TNF or TNF) treatment to asses the responsiveness to an anti-TNF treatment which comprises the detection of immunoglobulin(s) against one or more biomarker proteins in a bodily fluid or an excrement of said patient, and sorting the individual into one of two categories based on detection of said immunoglobulin(s), wherein individuals are classified as NON-responder or responder. The invention refers to diagnostic kits comprising said one or more biomarker proteins and the use of these kits for assessing the responsiveness to an anti-TNF treatment of an individual who is to be subjected to or is being subjected to an anti-TNF treatment.

Provided herein are methods, kits, and pharmaceutical compositions that include a PI3 kinase inhibitor for treating cancers or hematologic disorders.

The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Receptor Tyrosine-Protein Kinase erbB-3, or Her3 , that are particularly advantageous for quantifying the Her3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue reagents and protocol and the Her3 protein is quantitated in the Liquid Tissue sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of a Her3 peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

The present disclosure provides methods and kits for identifying and treating individuals at risk of or suffering from amyloid transthyretin cardiomyopathy. In general, detection or measurement of one or more biomarkers, such as TnI, PKM1, PKM2, NT-proBNP, RBP4, DCN, TIMP2, SMOC-2, NfL, or combinations thereof, assists in the identification of amyloid transthyretin cardiomyopathy. The present disclosure also provides methods for selecting patients for treatment of amyloid transthyretin cardiomyopathy, such as with transthyretin stabilizing agents.

Receptor protein kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating formation of complexes that regulate key cellular functions. Over 5 half of the known tyrosine kinases are implicated in human cancers and are therefore highly promising drug targets. A large-scale loss-of-function analysis of tyrosine kinases using RNA interference in the clinically relevant Erb-B2 positive, BT474 breast cancer cell line showed that Bruton's tyrosine kinase (BTK), a cytosolic, non-receptor tyrosine kinase that has been extensively studied for its role in B cell development, is required, in altered form, for BT474 10 breast cancer survival. This alternative form contains an amino-terminal extension that is also present in tumorigenic breast cells at significantly higher levels than in normal breast cells.

Provided herein are methods, kits, and pharmaceutical compositions that include a PI3 kinase inhibitor for treating cancers or hematologic disorders.

Receptor protein kinases (RPTKs) transmit extracellular signals across the plasma membrane to cytosolic proteins, stimulating formation of complexes that regulate key cellular functions. Over half of the known tyrosine kinases are implicated in human cancers and are therefore highly promising drug targets. A large-scale loss-of-function analysis of tyrosine kinases using RNA interference in the clinically relevant Erb-B2 positive, BT474 breast cancer cell line showed that Bruton's tyrosine kinase (BTK), a cytosolic, non-receptor tyrosine kinase that has been extensively studied for its role in B cell development, is required, in altered form, for BT474 breast cancer survival. This alternative form contains an amino-terminal extension that is also present in tumorigenic breast cells at significantly higher levels than in normal breast cells. Thus, embodiments of the invention find application in the field of cancer therapy.

The invention relates to methods and compositions for regulation of GSK3 activity. The invention provides phosphorylated GSK3 polypeptides and antibodies that recognize such polypeptides The invention further includes methods for treating disorders that are associated with elevated or reduced GSK3 activity.

The present invention provides methods for detecting, measuring and quantitating the activation states of components of the PI3K signaling pathway in cells such as tumor cells. In particular embodiments, the present invention enable the determination of tumor adaptation to anticancer therapy. Accordingly, the present invention provides methods for improved cancer therapy selection/adjustment and disease monitoring.

Certain imidazopyrazines and pharmaceutical compositions thereof are provided herein. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of Syk activity, which comprises administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are provided. Also provided are methods for determining the presence or absence of Syk kinase in a sample.