Skip NavigationSkip to Content
Return Return to Search Results

Targeted Mass Spectrometry Enables Quantification of Novel Pharmacodynamic Biomarkers of ATM Kinase Inhibition

  1. Author:
    Whiteaker, Jeffrey R [ORCID]
    Wang, Tao
    Zhao, Lei
    Schoenherr, Regine M
    Kennedy, Jacob J
    Voytovich, Ulianna
    Ivey, Richard G
    Huang, Dongqing
    Lin, Chenwei
    Colantonio,Simona
    Caceres,Tessa
    Roberts,Rhonda
    Knotts,Joseph
    Kaczmarczyk,Jan
    Blonder,Josip
    Reading,Joshua
    Richardson, Christopher W
    Hewitt, Stephen M
    Garcia-Buntley,Stephanie
    Bocik,William
    Hiltke, Tara
    Rodriguez, Henry
    Harrington, Elizabeth A
    Barrett, J Carl
    Lombardi, Benedetta
    Marco-Casanova, Paola
    Pierce, Andrew J [ORCID]
    Paulovich, Amanda G

  2. Author Address

    Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA 98109, USA., Cancer Research Technology Program, Antibody Characterization Lab, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, USA., Experimental Pathology Laboratory, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA., Office of Cancer Clinical Proteomics Research, National Cancer Institute, Bethesda, MD 20892, USA., Translational Sciences, Oncology, AstraZeneca, Cambridge CB4 0WG, UK.,
    1. Year: 2021
    2. Date: Aug
    3. Epub Date: 2021 07 30
  2. Journal: Cancers
    1. 13
    2. 15
  4. Type of Article: Article
  5. Article Number: 3843
  6. ISSN: 2072-6694
  1. Abstract:

    The ATM serine/threonine kinase (HGNC: ATM) is involved in initiation of repair of DNA double-stranded breaks, and ATM inhibitors are currently being tested as anti-cancer agents in clinical trials, where pharmacodynamic (PD) assays are crucial to help guide dose and scheduling and support mechanism of action studies. To identify and quantify PD biomarkers of ATM inhibition, we developed and analytically validated a 51-plex assay (DDR-2) quantifying protein expression and DNA damage-responsive phosphorylation. The median lower limit of quantification was 1.28 fmol, the linear range was over 3 orders of magnitude, the median inter-assay variability was 11% CV, and 86% of peptides were stable for storage prior to analysis. Use of the assay was demonstrated to quantify signaling following ionizing radiation-induced DNA damage in both immortalized lymphoblast cell lines and primary human peripheral blood mononuclear cells, identifying PD biomarkers for ATM inhibition to support preclinical and clinical studies.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.3390/cancers13153843
  3. PMID: 34359745
  4. View record in Web of Science®
  5. WOS: 000681856400001
  6. PII : cancers13153843

Library Notes

  1. Fiscal Year: FY2020-2021
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel