Clinical translation of a NexGen platform for quantifying protein networks in human biospecimens

用于量化人类生物样本中蛋白质网络的 NexGen 平台的临床转化

• 批准号: 10657403
• 负责人: AMANDA G PAULOVICH
• 金额: $ 69.28万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10657403
• 关键词: Analytical Chemistry; Antibodies; Antibody Specificity; Biological Assay; Biomedical Engineering; Blood Cells; Calibration; Clinical; Clinical Chemistry; Clinical Trials; Collaborations; Communities; Complement; Conduct Clinical Trials; DNA Damage; Data; Development; Dose; Ensure; Environment; Enzyme-Linked Immunosorbent Assay; Formalin; Freezing; Genomics; Goals; Guidelines; Heterogeneity; Human; Immunoassay; Immunohistochemistry; Industrialization; Industry; Laboratories; Leadership; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Measurement; Methods; Modernization; National Cancer Institute; Pathologist; Pathology; Pathway interactions; Patient Selection; Performance; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pharmacodynamics; Pharmacotherapy; Phase; Phosphotransferases; Process; Protein Biochemistry; Proteins; Proteome; Proteomics; Protocols documentation; Reagent; Research Personnel; Sampling; Schedule; Shipping; Signal Transduction; Site; Standardization; Technology; Testing; Tissues; Translating; Translations; Tumor Suppressor Proteins; Validation; Variant; Western Blotting; Work; cancer therapy; clinical translation; driver mutation; drug candidate; drug development; drug discovery; early phase clinical trial; early phase trial; experience; improved; innovation; multidisciplinary; multiple reaction monitoring; multiplex assay; next generation; novel; novel anticancer drug; novel therapeutics; open source; pre-clinical; precision oncology; response; small molecule; statistics; targeted cancer therapy; targeted treatment; tissue fixing; treatment response; tumor

Project Summary/Abstract Due to technological limitations, there are no validated assays for quantifying the majority of human proteins in clinical biospecimens, and thus most of the human proteome is clinically inaccessible. Because most modern cancer therapies act on proteins, our inability to quantify proteins is an impediment to the translation of targeted therapies. Furthermore, proteins act as interconnected “networks,” and thus we must be able to quantify panels of proteins in cancers to assess the activity of pathways and networks that determine treatment responses. Our project aims to translate (for use in clinical trial settings) a multiplex protein assay for quantifying tumor suppressor proteins and cell signaling networks that response to DNA damage- a critical network targeted by current drug discovery efforts. The assay is based on a NextGen platform for quantifying protein panels uses targeted, multiple reaction monitoring mass spectrometry (MRM-MS), which complements existing protein assay technologies and overcomes many of the technological limitations, including enabling multiplexing of assays for many proteins in a single network. MRM has been extensively validated in the preclinical space but has not yet been adapted for clinical trials. Our multidisciplinary team brings together academic partners with diverse expertise (MRM-MS, analytical chemistry, clinical chemistry, pathology, statistics, bioengineering, protein biochemistry) with an industrial partner (AstraZeneca) that has extensive experience in drug development and clinical trials. Successful adaptation of this MRM-based assay panel to the clinical trial setting will provide a road map and standard operating protocols (SOPs) for translation of additional MRM-based assay panels (>1,500 assays are already publicly available at https://assays.cancer.gov/).

项目总结/文摘

项目成果

Phase I/II results of ceralasertib as monotherapy or in combination with acalabrutinib in high-risk relapsed/refractory chronic lymphocytic leukemia.

• DOI: 10.1177/20406207231173489
• 发表时间: 2023
• 期刊: THERAPEUTIC ADVANCES IN HEMATOLOGY
• 影响因子: 3.4
• 作者: Jurczak, Wojciech;Elmusharaf, Nagah;Fox, Christopher P.;Townsend, William;Paulovich, Amanda G.;Whiteaker, Jeffrey R.;Krantz, Fanny;Wun, Chuan-Chuan;Parr, Graeme;Sharma, Shringi;Munugalavadla, Veerendra;Manwani, Richa;Dean, Emma;Munir, Talha
• 通讯作者: Munir, Talha