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: 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: 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 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.

Abstract: The current disclosure provides for a specific peptide, and derived ionization characteristics of a peptide from the tubulin beta-3 chain protein (TUBB3) that is particularly advantageous for quantifying the TUBB3 protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry. A protein sample is prepared from a biological sample using the Liquid Tissue reagents and protocol and the TUBB3 protein is quantitated by SRM/MRM mass spectrometry analysis of the sample, where the specific peptide is quantitated. Methods of treatment are provided in which the measured level of TUBB3 in a patient tumor sample is compared with a reference level and the patient is treated with a taxane-based treatment regimen when the measured TUBB3 level is lower than the reference level. A suitable reference level is, for example, about 700 amol/?g tissue.

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: Methods are provided for quantifying specific proteins 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 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 or more of the described peptides.