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.

The invention provides to PKN1 gene fusions, PKN1 fusion proteins, and fragments of those genes and polypeptides. The invention further provides methods of diagnosing and treating diseases or disorders associated with PKN1 fusions, such as conditions mediated by aberrant PKN1 expression or activity, or over expression of PKN1.

The present invention relates to the diagnosis of colorectal cancer. It discloses the use of protein S100A12 in the diagnosis of colorectal cancer. It relates to a method for diagnosis of colorectal cancer from a stool sample, derived from an individual by measuring S100A12 in said sample. Measurement of S100A12 can, e.g., be used in the early detection or diagnosis of colorectal cancer.

The invention provides the identification of the presence of mutant ROS protein in human cancer. In some embodiments, the mutant ROS are FIG-ROS fusion proteins comprising part of the FIG protein fused to the kinase domain of the ROS kinase. In some embodiments, the mutant ROS is the overexpression of wild-type ROS in cancerous tissues (or tissues suspected of being cancerous) where, in normal tissue of that same tissue type, ROS is not expressed or is expressed at lower levels. The mutant ROS proteins of the invention are anticipated to drive the proliferation and survival of a subgroup of human cancers, particularly in cancers of the liver (including bile duct), pancreas, kidney, and testes. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS polypeptides (e.g., a FIG-ROS(S) fusion polypeptide), probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The identification of the mutant ROS polypeptides enables new methods for determining the presence of these mutant ROS polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

Disclosed herein are novel antibodies specific to Tnk1 or variants thereof. Also disclosed are methods of using such antibodies. The methods include therapeutic methods against certain types of cancers or infections involving administration of novel antibodies or fragments thereof. Also, methods of using highly selective antibodies for detecting aberrant Tnk1 or functionally deficient Tnk1.

A biological process indicator is provided for validating a treatment process in which the amount or activity of a contaminant in a sample is reduced. The indicator comprises a thermostable kinase covalently linked to a biological component, with the proviso that the biological component is not an antibody. Methods of preparing the indicator, and methods of using the indicator, are also provided.

Certain pyrazolo[1,5-a]pyrimidines: ##STR00001##
or pharmaceutically acceptable salts thereof, 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.

The invention provides assay particles useful, for example, for detecting analytes and binding molecule interactions. One type of assay particle includes a core portion encased by a shell portion, wherein the shell portion comprises an inorganic phosphor that binds selectively to a target molecule. Another type of an assay particle includes a core portion encased by a shell portion, and a coat portion covering the shell portion, wherein the coat portion comprises an inorganic phosphor that binds selectively to a target molecule. A further type of assay particle includes a core portion encased by a shell portion, and a coat portion covering the shell portion, wherein the coat portion comprises an inorganic phosphor and a target selective binding moiety, and wherein the assay particle is buoyant in aqueous media. An additional type of assay particle includes a core portion encased by a shell portion, and a coat portion covering the shell portion, wherein the shell portion comprises an inorganic phosphor and the coat portion comprises a target selective binding moiety, and wherein the assay particle is buoyant in aqueous media. Also provided are kits and related methods.

Provided herein are methods for treating a cancer treatable by inhibition of phosphorylation of PRAS40, GSK3 or p70S6K1, comprising administering an effective amount of a TOR kinase inhibitor to a patient having a cancer treatable by inhibition of phosphorylation of PRAS40, GSK3 or p70S6K1.

The invention relates to biomarkers and methods of diagnosing or monitoring schizophrenia, or a predisposition thereto.