A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents

Raman spectroscopy is a non-invasive and label-free optical technique that provides detailed information about the molecular composition of a sample. In this study, we evaluated the potential of Raman spectroscopy to predict skin toxicity due to tyrosine-kinase inhibitors treatment. We acquired Raman spectra of skin of patients undergoing treatment with MEK, EGFR or BRAF inhibitors which are known to induce severe skin toxicity; for this pilot study, three patients were included for each inhibitor. Our algorithm, based on Partial Least Squares-Discriminant Analysis (PLS-DA) and cross-validation by bootstrapping, discriminated to variable degrees spectra from patient suffering and not suffering cutaneous adverse events. For MEK and EGFR inhibitors, discriminative power was over 90% in the viable epidermis skin layer, whereas for BRAF inhibitors, discriminative power was 71%. There was a 81.5% correlation between whole blood drug concentration and Raman signature of skin in the case of EGFR inhibitors and viable epidermis skin layer. Our results demonstrate the power of Raman spectroscopy to detect apparition of skin toxicity in patients treated with tyrosine-kinase inhibitors at levels not detectable via dermatological inspection and histological evaluation.