Abstract: The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFR?) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFR? is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFR?-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFR? is expressed, and for determining whether a compound inhibits the progression of a PDGFR?-expressing mammalian NSCLC tumor.

Abstract: The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFR?) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFR? is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFR?-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFR? is expressed, and for determining whether a compound inhibits the progression of a PDGFR?-expressing mammalian NSCLC tumor.

Abstract: The invention discloses a previously unidentified subset of mammalian non-small cell lung carcinomas (NSCLC) in which platelet-derived growth factor receptor alpha (PDGFR?) is expressed and is driving the disease, and provides methods for identifying a mammalian NSCLC tumor that belongs to a subset of NSCLC tumors in which PDGFR? is expressed, and for identifying a NSCLC tumor that is likely to respond to a PDGFR?-inhibiting therapeutic. The invention also provides methods for inhibiting the progression of a mammalian NSCLC tumor in which PDGFR? is expressed, and for determining whether a compound inhibits the progression of a PDGFR?-expressing mammalian NSCLC tumor.

Abstract: The invention discloses two newly-discovered Flt3 phosphorylation sites, tyrosine 589 (Tyr589) and tyrosine 591 (Tyr591) in the intracellular domain, and provides antibodies, both polyclonal and monoclonal, that selectively bind to Flt3 when phosphorylated at these novel sites. Also provided are assays utilizing these reagents, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibodies, that binds to Flt3 when phosphorylated at Tyr589 or Tyr591. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).

Abstract: The invention provides monoclonal antibodies that bind the estrogen receptor ? (ER ?) when phosphorylated at serine 118 (Ser118) in the N-terminal domain, but do not bind to ER ? when not phosphorylated at this site. Also provided are methods for determining the phosphorylation of ER ? in a biological sample, profiling ER ? activation in a test tissue, and identifying a compound that modulates phosphorylation of ER ? in a test tissue, by using the disclosed monoclonal antibodies. The sample or test tissue may be taken from a subject suspected of having cancer, such as breast cancer. Kits comprising the phospho-ER ? (Ser118) monoclonal antibodies of the invention are also provided.

Abstract: The invention disclosed herein provides methods for the examination and/or quantification of biochemical pathways that are disregulated in pathologies such as cancer and to reagents and kits adapted for performing such methods.

Abstract: The invention discloses two newly-discovered Flt3 phosphorylation sites, tyrosine 589 (Tyr589) and tyrosine 591 (Tyr591) in the intracellular domain, and provides antibodies, both polyclonal and monoclonal, that selectively bind to Flt3 when phosphorylated at these novel sites. Also provided are assays utilizing these reagents, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibodies, that binds to Flt3 when phosphorylated at Tyr589 or Tyr591. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).

Abstract: The present invention provides methods for identifying the most relevant signal transduction pathway biomarkers of disease progression, outcome, or therapeutic responsiveness, using phospho-specific antibodies in cellular assays to identify proteins whose activity is correlated to the relevant outcome (e.g. therapeutic responsiveness). The invention also provides a method for utilizing correlated biomarker(s) to predict patient response to a therapeutic composition having efficacy against a disease involving altered signal transduction by employing one or more phospho-specific antibodies to detect activation status of such biomarker(s) in cellular assays. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides novel reagents and methods for detecting BCR-ABL or c-Abl kinase activity, and/or Abl signaling pathway activation in a cell or tissue, and discloses novel biomarkers relevant to Abl-mediated disease progression and therapeutic responsiveness, and provides predictive and detection methods based on the same. Phosphorylated BCR-ABL (Tyr245) and/or c-Abl (Tyr245), BCR-ABL (Tyr735) and/or c-Abl (Tyr735), Bcr (Tyr177), CRKL (Tyr207), Gab1 (Tyr627), PYK2 (Tyr402), Tyk2 (Tyr1054/1055), SHP2 (Tyr580), ERK1/2 (Thr202/Tyr204) and MEK1/2 (Ser217/221) have now been identified as relevant biomarkers of c-Abl pathway-mediated disease, and phospho-specific antibodies to these targets are provided. Kits for carrying out the methods of the invention are also provided.

Abstract: The invention provides monoclonal antibodies that bind the estrogen receptor &agr; (ER &agr;) when phosphorylated at serine 118 (Ser118) in the N-terminal domain, but do not bind to ER &agr; when not phosphorylated at this site. Also provided are methods for determining the phosphorylation of ER &agr; in a biological sample, profiling ER &agr; activation in a test tissue, and identifying a compound that modulates phosphorylation of ER &agr; in a test tissue, by using the disclosed monoclonal antibodies. The sample or test tissue may be taken from a subject suspected of having cancer, such as breast cancer. Kits comprising the phospho-ER &agr; (Ser118) monoclonal antibodies of the invention are also provided.