A strategy for early detection of response to chemotherapy drugs based on treatment-related changes in the metabolome
Authors
Amin, SRattner, 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, CanadaIssue Date
2019
Metadata
Show full item recordAbstract
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 OneDOI
10.1371/journal.pone.0213942PubMed ID
30939138Additional Links
https://dx.doi.org/10.1371/journal.pone.0213942Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0213942