Abstract: The present invention relates to a method of using family and/or regulatory members of the PD-1/PD-L1 pathway as predictive markers for risk of skin cancer development and as targets for therapeutic prevention of pre-malignant (or pre-cancerous) skin lesions and non-melanoma skin cancer (NMSC). This invention will allow for quantitative measurements of UV-induced expression of PD-1/PD-Li signaling pathway family members (e.g., PD-1, PD-L1, PD-L2) and/or PD-1/PD-L1 regulatory factors including AP-1 and NF?B family members in skin tissue of individuals to determine an individual's 1) risk for skin cancer development and 2) appropriate prophylactic treatment strategy to prevent skin cancer development. This information will facilitate identification of those patients at risk for pre-malignant (or pre-cancerous) skin lesions or subsequent NMSC lesions who would benefit from a PD-1/PD-L1 pathway suppressing therapy to prevent skin cancer development.

Abstract: An assay device for determining the presence of analytes in a cell lysate comprises a porous support member and a plurality of binding reagents arranged and immobilized at multiple reaction sites on the support member. The binding reagents are selected and arranged to assess the status of a selected cellular signal transduction pathway/protein-protein interactive network. In a further aspect, a method for assessing the status of a signal transduction pathway comprises generating a lysate of cells, the lysate retaining one or more pathway molecules present in one or more states and the pathway molecules reflecting signal transduction events taking place in the cells. The method further includes applying the lysate to an immobilized series of binding reagents which can discriminate the pathway molecules and their states. Binding events between the pathway molecules and the binding reagents are identified and the state of the selected signal pathway is determined.

Abstract: An assay device for determining the presence of analytes in a cell lysate comprises a porous support member and a plurality of binding reagents arranged and immobilized at multiple reaction sites on the support member. The binding reagents are selected and arranged to assess the status of a selected cellular signal transduction pathway/protein-protein interactive network. In a further aspect, a method for assessing the status of a signal transduction pathway comprises generating a lysate of cells, the lysate retaining one or more pathway molecules present in one or more states and the pathway molecules reflecting signal transduction events taking place in the cells. The method further includes applying the lysate to an immobilized series of binding reagents which can discriminate the pathway molecules and their states. Binding events between the pathway molecules and the binding reagents are identified and the state of the selected signal pathway is determined.

Abstract: The present invention provides reliable methods to identify subsets of subjects with a cancer of epithelial origin characterized by a high level of phosphorylated c-erbB2 which does not correlate with the over-expression of total c-erbB2 as measured by IHC or FISH, for selection and inclusion for c-erbB2-direct treatment and therapy. Furthermore, the present invention provides a reliable method to determine whether a subject with a cancer of epithelial origin who has been determined to be c-erbB2 positive by IHC and by FISH should be excluded from c-erbB2-direct treatment because of a non-significant level of phosphorylated c-erbB2 in epithelial tumor tissue.

Abstract: Disclosed herein are: 1) methods for determining the appropriate drug therapy for a patient with colorectal cancer that has metastasized to the patient's liver and/or lung; 2) methods for treating such a patient; and 3) pharmaceutical compositions for such treatment.

Abstract: An immunoassay device incorporating porous polymeric capture nanoparticles within either the sample collection vessel or pre-impregnated into a porous substratum within fluid flow path of the analytical device is presented. This incorporation of capture particles within the immunoassay device improves sensitivity while removing the requirement for pre-processing of samples prior to loading the immunoassay device. A preferred embodiment is coreshell bait containing capture nanoparticles which perform three functions in one step, in solution: a) molecular size sieving, b) target analyte sequestration and concentration, and c) protection from degradation. The polymeric matrix of the capture particles may be made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle.

Abstract: A method for selecting combinations of drugs for treatment of diseases that arise from deranged signaling pathways is disclosed. The method involves measuring the activity states for signaling proteins in a diseased cell and determining whether the activity states are different from the activity states observed for a reference cell such as a normal cell. Based on the observed differences, combinations of two or more drugs are selected to reduce these differences. Treatment of a subject with the combinations restores the activity states of the signaling proteins of the deranged disease-associated signaling pathways toward the activity states observed in the reference cell. Since the diseased cell and the reference cell can both be obtained from the same subject, combinations of drugs that specifically target patient-specific signaling derangements is possible.

Abstract: Methods are provided for treating cancer metastasis by administering a therapeutic composition targeting a kinase substrate cascade.

Abstract: The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.

Abstract: This invention relates, e.g., to a method for predicting a subject's response to a chemotherapeutic agent and/or the subject's prognosis, comprising measuring the phosphorylation state of at least one member of the mTOR pathway, and/or of at least one member of an interconnected polypeptide pathway (e.g. a member of the Akt pathway or a member of the IRS pathway), compared to a baseline value, in a cancer tissue or cancer cell sample from the subject, wherein an elevated level of the phosphorylation state compared to the baseline value indicates that the subject is a non-responder to the chemotherapeutic agent and/or has a poor prognosis. Also described is a method for treating a cancer in a subject in need thereof, wherein the subject exhibits an elevated level of the phosphorylation state, comprising administering one or more inhibitors of the mTOR and/or an interconnected pathway.

Abstract: A method for selecting combinations of drugs for treatment of diseases that arise from deranged signaling pathways is disclosed. The method involves measuring the activity states for signaling proteins in a diseased cell and determining whether the activity states are different from the activity states observed for a reference cell such as a normal cell. Based on the observed differences, combinations of two or more drugs are selected to reduce these differences. Treatment of a subject with the combinations restores the activity states of the signaling proteins of the deranged disease-associated signaling pathways toward the activity states observed in the reference cell. Since the diseased cell and the reference cell can both be obtained from the same subject, combinations of drugs that specifically target patient-specific signaling derangements is possible.

Abstract: Methods of selecting a treatment for a patient with multiple myeloma are provided. Prior to commencing a treatment regime, bone marrow aspirates are isolated from a patient and incubated with one or more candidate therapeutics. The methods identify the therapy or combination of therapies most likely to yield the best results for a particular individual. In addition to improving clinical outcome, such theranostic evaluations dramatically reduce health care costs, by avoiding ineffective therapies. Screening assays for identifying treatments for multiple myeloma also are provided.

Abstract: The present invention relates to the identification and diagnostic use of biomarkers in primary colorectal cancer tumors whose activation level are predictive of the likelihood of the onset of metastatic disease. These biomarkers may be used to determine the suitability of a patient for aggressive and/or targeted treatments. Kits and compositions of the invention are also provided.

Abstract: The present invention provides reliable methods to identify subsets of subjects with a cancer of epithelial origin characterized by a high level of phosphorylated c-erbB2 which does not correlate with the over-expression of total c-erbB2 as measured by IHC or FISH, for selection and inclusion for c-erbB2-direct treatment and therapy. Furthermore, the present invention provides a reliable method to determine whether a subject with a cancer of epithelial origin who has been determined to be c-erbB2 positive by IHC and by FISH should be excluded from c-erbB2-direct treatment because of a non-significant level of phosphorylated c-erbB2 in epithelial tumor tissue.

Abstract: This invention relates, e.g., to a method for predicting the response of a subject having, or at risk of developing, breast cancer to Tamoxifen therapy. The method comprises measuring the amount of phosphorylation at residues S70 of Bcl-2, Y992 of EGFR, and/or Y527 of Src in a suitable sample from the subject, wherein a statistically significantly elevated level of phosphorylation at one or more of the three residues compared to a baseline value indicates that the subject is likely to be responsive to Tamoxifen therapy.

Abstract: This invention relates, e.g., to a set of calibrants for determining the amount in a sample of an analyte (e.g., a protein, such as a protein that has been post-translationally modified), comprising a plurality of calibrants, which contain a range of amounts (e.g., defined amounts and/or serial dilutions) of the analyte, spanning the expected amount of the analyte in the sample. In each of the calibrants, a defined amount of the analyte is present in the same suitable, biological diluent (e.g., a cell or tissue lysate, or a bodily fluid). In one embodiment of the invention, the diluent reflects the same or a similar biological milieu (proteins, lipids, serum proteins, serum matrix proteins, etc.) as that in the sample in which the analyte to be measured is present. In embodiments of the invention, a single calibrant (e.g., a cell lysate) may comprise as many as hundreds of analytes, and can be used for the quantification of those hundreds of analytes in a sample.

Abstract: Low molecular weight (LMW) peptides have been discovered that are indicative of breast cancer. Evaluating patient samples for the presence of such LMW peptides is an effective means of detecting breast cancer and monitoring the progression of the disease, for example during treatment. The LMW peptides are particularly useful in detecting breast cancer during its early stages.

Abstract: Methods are provided for treating cancer metastasis by administering a therapeutic composition targeting a kinase substrate cascade.

Abstract: This invention relates, e.g., to a method for predicting the prognosis, the likelihood of metastasis in, or the desirability of administering an aggressive therapy to, a subject with colorectal cancer, comprising determining, in a sample from the subject, the level of phosphorylation compared to a positive and/or negative reference standard, of one or more of: (a) AKT (S473); (b) BAD (S112); (c) cABL (T735); (d) ERK (T42/44); (e) MARCKS (S152-156); (0 p38MAPK (T180-182): (g) STAT 1 (Y701 ); (h) PTEN (S380); (i) EGFR (Y992); (j) PAK 1/2 (S 1 19/204); or (k) PKC zeta/lambda (T410-403); or the total amount of (1) COX-2 protein; wherein if the level of phosphorylation of one or more of a-i or the total amount of COX-2 protein (1) is elevated compared to the negative reference standard, and/or if the level of phosphorylation of j or k is decreased compared to the positive reference standard, the subject has poor prognosis, is likely to undergo metastasis, and/or is a good candidate for aggressive therapy.

Abstract: Provided are methods of identifying a metabolic target in a cancer stem cell that include using a microarray to identify intracellular signaling networks within a population of cancer stem cells that respond to a growth factor for the stem cell. Also provided are methods of determining a personalized therapeutic regime that include receiving metabolic information relating to a cancer stem cell in a patient, determining the patient's personal criteria relevant to the therapeutic regime, and combining the metabolic and personal criteria. Also provided are a diagnostic test for establishing a personalized therapeutic regime for a colon cancer patient and methods of reducing colon cancer stem cells/treating colon cancer.