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Metabolites 2017, 7(4), 60;

Monitoring for Response to Antineoplastic Drugs: The Potential of a Metabolomic Approach

Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB T2N 4N2, Canada
Department of Surgery, Tom Baker Cancer Center, University of Calgary, 1331 29th St NW, Calgary, AB T2N 4N2, Canada
Department of Oncology, Tom Baker Cancer Center, University of Calgary, 1331 29th St NW, Calgary, AB T2N 4N2, Canada
Author to whom correspondence should be addressed.
Received: 28 August 2017 / Revised: 9 October 2017 / Accepted: 13 November 2017 / Published: 16 November 2017
(This article belongs to the Special Issue Metabolomics and/or Biomarkers for Drug Discovery)
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For most cancers, chemotherapeutic options are rapidly expanding, providing the oncologist with substantial choices. Therefore, there is a growing need to select the best systemic therapy, for any individual, that effectively halts tumor progression with minimal toxicity. Having the capability to predict benefit and to anticipate toxicity would be ideal, but remains elusive at this time. An alternative approach is an adaptive approach that involves close observation for treatment response and emergence of resistance. Currently, response to systemic therapy is estimated using radiographic tests. Unfortunately, radiographic estimates of response are imperfect and radiographic signs of response can be delayed. This is particularly problematic for targeted agents, as tumor shrinkage is often not apparent with these drugs. As a result, patients are exposed to prolonged courses of toxic drugs that may ultimately be found to be ineffective. A biomarker-based adaptive strategy that involves the serial analysis of the metabolome is attractive. The metabolome changes rapidly with changes in physiology. Changes in the circulating metabolome associated with various antineoplastic agents have been described, but further work will be required to understand what changes signify clinical benefit. We present an investigative approach for the discovery and validation of metabolomic response biomarkers, which consists of serial analysis of the metabolome and linkage of changes in the metabolome to measurable therapeutic benefit. Potential pitfalls in the development of metabolomic biomarkers of response and loss of response are reviewed. View Full-Text
Keywords: chemotherapy; metabolomics; response; therapeutic benefit chemotherapy; metabolomics; response; therapeutic benefit

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Rattner, J.; Bathe, O.F. Monitoring for Response to Antineoplastic Drugs: The Potential of a Metabolomic Approach. Metabolites 2017, 7, 60.

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