Background: Only a fraction of patients benefit from any given chemotherapeutic. An assay that enables early identification of individuals who are/are not benefiting from a drug would be useful. We postulate that a response to systemic therapy is associated with characteristic changes in extracellular metabolites.

Methods: Multiple tumor cell lines were exposed to a variety of chemotherapeutics. Supernatants collected at baseline and at 72 hours were analyzed by gas chromatography-mass spectrometry to identify metabolomic changes. An MTT assay was used to quantify growth inhibition.

Results: We identified 23 candidate metabolites that change with response to therapy, independent of cell and drug type. This model had a sensitivity and specificity of 0.714 and 0.813 respectively in an ROC analysis.

Conclusions: The candidate metabolites identified will be assessed in clinical samples from patients treated with systemic therapy. Identification of response-related changes in the circulating metabolome may represent a novel means of detecting response to chemotherapy.