Abstract: The present invention provides variant VEGF polypeptides which have been altered in their C-terminal heparin binding region to lower their heparin binding affinity. These variants have been found to act as receptor antagonists for VEGF receptors and antagonize angiogenesis. These variants are useful to treat diseases characterized by pathological angiogenesis.

Abstract: Methods are provided for identifying whether a cancer patient, and especially a breast cancer patient, will be responsive to treatment. Specified TOPO2A, IDO1 and/or p16 fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in cancer cells collected from tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the cancer patient will positively respond to treatment. Measurement of TOPO2A provides a direct indication of whether a patient will respond to anthracycline-containing therapy, and, in particular, neoadjuvant anthracycline-containing therapy. Quantitative levels of IDO1 and p16 are compared to reference levels in order to determine if a breast cancer patient will likely demonstrate a pathologically complete response (pCR) of cancer after cancer therapy treatment, irrespective of the chosen treatment.

Abstract: Methods are provided for identifying whether a tumor, and especially a colon tumor, will be responsive to treatment with the therapeutic agent temozolomide. A specific MGMT fragment peptide is precisely detected and quantitated by SRM-mass spectrometry directly in colon cancer cells collected from colon tumor tissue obtained from a cancer patient. Comparison to reference levels determines if the cancer patient will respond positively or negatively to treatment with the chemotherapeutic agent temozolomide.

Abstract: A method is provided for quantifying the UCK2 protein in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry and utilizing said quantitation of UCK2 to predict the therapeutic outcome of treating a colon cancer patient with the combinatorial FOLFOX (5-fluorouracil, folinic acid, and oxaliplatin) treatment regimen.

Abstract: Methods are provided herein for identifying whether a cancer patient, for example a colorectal cancer patient, will be responsive to treatment with a therapeutic strategy comprising administration of the FOLFOX regimen (5-fluorouracil, leucovorin, and oxaliplatin). Specified TYMP and UCK2 fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in tumor cells, for example colorectal cancer tumor cells, that are collected from tumor tissue obtained from a cancer patient and compared to reference levels in order to determine if the cancer patients will positively respond to treatment with the combination treatment of FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin).

Abstract: Improved methods for treating cancer are provided herein by determining if a cancer patient, particularly a colon cancer patient or a gastric cancer patient, will clinically respond in a favorable manner to a therapeutic strategy comprising the FOLFOX regimen (fluorouracil, leucovorin, and oxaliplatin) or a combination of capecitabine and cisplatin. Diagnostic methods for measuring the OPRT, TYMP, and/or UCK2 proteins in a tissue sample, such as a tumor sample, from the patient are provided.

Abstract: Methods are provided for treating a cancer patient suffering from a glioblastoma (GBM) by administering to the patient an effective amount of temozolomide, wherein a mass spectrometry analysis of a protein digest of a formalin-fixed tumor sample from the patient evidences an amount of a MGMT fragment peptide less than or substantially equal to 150 amol/?g.

Abstract: Methods are provided for identifying colon cancer patients whose genome shows either microsatellite stability (MSS) and/or a low tumor mutational burden (TMB) with a good prognosis, irrespective of treatment strategy. Specific protein fragment peptides of the p16 protein are precisely detected and quantitated by SRM-mass spectrometry directly in MSS and/or low TMB colon tumor cells collected from colon tumor tissue that was obtained from a colon cancer patient. The measured p16 levels are compared to p16 reference levels to determine if the MSS and/or low TMB colon cancer patient will have a longer overall survival.

Abstract: Methods are provided for identifying whether a tumor, and especially a lung tumor, will be responsive to treatment with a therapeutic regimen that contains a platinum-based agent such as cisplatin and optionally contains a taxane. A specific Schlafen family member 11 (SLFN11) fragment peptide is precisely detected and quantitated by spectrometry directly in lung cancer cells collected from lung tumor tissue obtained from a cancer patient. Comparison to reference levels determines if the cancer patient will respond positively or negatively to treatment with the chemotherapeutic agents taxane plus a platinum-based agent such as cisplatin.

Abstract: Methods are provided for detecting and quantifying the DLL1, DLL3, JAG1, JAG2, Notch1, Notch 2, Notch 3, Notch 4, and/or DLL4 proteins in biological samples, such as a formalin fixed paraffin embedded tissue samples, using mass spectrometry. Additionally, methods are provided for treating cancer based upon the level of the DLL1, DLL3, JAG1, JAG2, Notch1, Notch 2, Notch 3, Notch 4, and/or DLL4 proteins in the biological samples.

Abstract: Methods are provided for identifying whether a lung tumor will be responsive to treatment with the combination of the therapeutic agents cisplatin and pemetrexed. Specified ERCC1, TS, p16, and FR? fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in lung tumor cells collected from lung tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with the combination of cisplatin and pemetrexed therapeutic agents.

Abstract: Improved methods for treating lung cancer are provided. Tumor samples from patients are analyzed (i) by DNA sequencing to detect the presence of HER2 mutations and (ii) by mass spectrometric proteomic analysis to determine whether HER2 protein is expressed in the tumor cells. Patients respond to therapy with trastuzumab emtansine (T-DM1) or an equivalent antibody-drug conjugate when unique HER2 protein fragments are detected in the patient's tumor cells that harbor HER2 mutations. Conversely, patients do not respond to T-DM1 therapy when the tumor cells contain HER2 mutations but the unique protein fragments are not detected. Detection of HER3 in the tumor cells is a positive predictor of response to treatment.

Abstract: Methods are provided for quantifying specific proteins directly in biological samples that have been fixed in formalin by SRM/MRM assay. 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. A protein digest is prepared from the biological sample using, for example, the Liquid Tissue reagents and protocol and a designated protein is quantitated in the digest sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the described peptides. The proteins that can be detected and/or quantitated are CD3D, B7H3, B7-2, STAT1, GBP1, GPNMB, CD27, CD3E, and CD8.

Abstract: SRM/MRM assays are used to detect and quantitate proteins involved in the process of initiating, inhibiting, maintaining, and/or otherwise modulating a tumor immune response directly in patient tumor tissue. The assays provide an immune profile of the tissue microenvironment, and may be used as part of improved methods of immune-based treatment using agents that manipulate the cancer immune response together with cancer therapeutic agents.

Abstract: Methods of treating breast cancer are provided where a quantitative Her2 assay is used to identify whether a breast tumor will be responsive to treatment with anti-Her2 therapeutic agents such as lapatinib and trastuzumab, followed by selection of a suitable treatment regimen and administration of the regimen. A specific Her2 fragment peptide is precisely quantitated by SRM-mass spectrometry directly in breast tumor cells collected from breast tumor tissue that was obtained from a cancer patient and compared to a reference level in order to determine if the breast cancer patient will positively respond to treatment with a therapeutic agent that specifically targets the Her2 protein.

Abstract: Methods are provided for quantifying the TYMS, TYMP, UCK1, UCK2, UPP1, OPRT, dCK, TK1, DPYD, CDA, RRM1, and/or RRM2 proteins directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring/Multiple Reaction Monitoring (SRM/MRM). The biological samples are chemically preserved 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 digest sample is prepared from the biological sample and the TYMS, TYMP, UCK1, UCK2, UPP1, OPRT, dCK, TK1, DPYD, CDA, RRM1, and/or RRM2 proteins are quantitated in the digest by SRM/MRM mass spectrometry.

Abstract: The present invention provides methods for treating cancer patients comprising assaying tumor tissue from patients and identifying those patients most likely to respond to treatment with a platinum-based agent, such as cisplatin, in combination with pemetrexed. Methods are provided for identifying those lung cancer patients most likely to respond to treatment with the combination of cisplatin+pemetrexed chemotherapy agents (“CDDP+PEM”) by determining expression patterns of a set of 38 specific proteins directly in tumor cells derived from patient tumor tissue using SRM mass spectrometry. The method further comprising determining if the patient will respond to treatment with combination therapy, and when proteomic analysis of patient tissue indicates that the patient will respond to treatment with combination therapy, the patient is administered a regimen that includes the pemetrexed/platinum agent combination.

Abstract: Methods are provided for identifying whether a tumor will be responsive to treatment with an anti-EGFR agent. Specific protein fragment peptides are precisely detected and quantitated by SRM-mass spectrometry directly in tumor cells collected from tumor tissue that was obtained from a cancer patient and compared to reference levels in order to determine if the lung cancer patient will positively respond to treatment with an anti-EGFR agent such as, for example, pamitumumab and/or erbitux.

Abstract: Methods are provided for quantifying CD56 and CHGA proteins directly in formalin-fixed biological samples by Selected Reaction Monitoring (SRM)/Multiple Reaction Monitoring (MRM) mass spectrometry. The biological samples may include formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, and FFPE tissue blocks and cells from those blocks. A protein sample may be prepared from said biological sample using the Liquid Tissue reagents and protocol and a designated 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 peptide fragment derived from each of the proteins.

Abstract: Methods are provided herein for using SRM/MRM assays to detect and quantitate proteins involved in all cellular processes including cell division, cellular differentiation, cell growth inhibition, cellular metabolism, cell signaling, and tumor immune response/modulation in a protein digest prepared from a biological sample of formalin fixed tumor tissue. The SRM/MRM assays can provide a tumor tissue profile of the entire tissue microenvironment, regardless of cellular origin of expression, which can provide an optimal cancer therapy treatment.