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    A strategy for early detection of response to chemotherapy drugs based on treatment-related changes in the metabolome

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    Authors
    Amin, S
    Rattner, J
    Keramati, M
    Farshidfar, F
    McNamara, Mairead G
    Knox, J
    Kopciuk, K
    Vogel, H
    Bathe, O
    Affiliation
    Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada
    Issue Date
    2019
    
    Metadata
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    Abstract
    We describe a biomarker-based approach to delivering chemotherapy that entails monitoring treatment changes in the circulating metabolome that reflect efficacy. In-vitro, multiple tumor cell lines were exposed to numerous chemotherapeutics. Supernatants were collected at baseline and 72 hours post treatment. MTT assays were used to quantify growth inhibition. Clinical samples were derived from a phase II clinical trial of second-line axitinib in patients with advanced hepatocellular carcinoma. Sera were collected at baseline and 2-4 weeks after treatment initiation. Response to therapy was estimated by CT scan at 8 weeks. Samples were analyzed by gas chromatography-mass spectrometry to identify metabolomic changes associated with response. In vitro, we found drug-specific and generalizable patterns of change in the extracellular metabolome accompany growth inhibition. A cell death signature was also identified. This approach was also applied to clinical samples. While the in vitro signatures were detectable in vivo, a more robust signal was identified clinically that appeared within 4 weeks of administering drug that distinguished individuals with a treatment response. These changes were extinguished as tumor growth resumed. Serial monitoring of the metabolome during chemotherapy is a means to follow treatment efficacy and emergence of resistance, informing the oncologist whether to modify treatment.
    Citation
    Amin S, Rattner J, Keramati MR, Farshidfar F, McNamara MG, Knox JJ, et al. A strategy for early detection of response to chemotherapy drugs based on treatment-related changes in the metabolome. PLoS One. 2019;14(4):e0213942.
    Journal
    PLoS One
    URI
    http://hdl.handle.net/10541/621760
    DOI
    10.1371/journal.pone.0213942
    PubMed ID
    30939138
    Additional Links
    https://dx.doi.org/10.1371/journal.pone.0213942
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0213942
    Scopus Count
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