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  • [Cancer Res. ] A Novel Spectroscopically Determined Pharmacodynamic Biomarker for Skin Toxicity in Cancer Patients Treated with Targeted Agents.

    CNRS / Antoine Azan*

  • 출처
    Cancer Res.
  • 등재일
    2017 Jan 15
  • 저널이슈번호
    77(2):557-565. doi: 10.1158/0008-5472.CAN-16-1733. Epub 2016 Nov 11.
  • 내용

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    Abstract

    Raman spectroscopy is a noninvasive 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 more than 90% in the viable epidermis skin layer; whereas for BRAF inhibitors, discriminative power was 71%. There was a 81.5% correlation between 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. 

     

    Author information

    Azan A1, Caspers PJ2,3, Bakker Schut TC2,3, Roy S4, Boutros C4, Mateus C4, Routier E4, Besse B4, Planchard D4, Seck A5, Kamsu Kom N6, Tomasic G7, Koljenović S8, Noordhoek Hegt V8, Texier M9, Lanoy E9, Eggermont AM4,10, Paci A11,5, Robert C4,6,10, Puppels GJ2,3, Mir LM11.

    1UMR 8203, CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France. antoine.azan@gustaveroussy.fr.

    2Center for Optical Diagnostics & Therapy, Department of Dermatology, Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.

    3RiverD International B.V. Rotterdam, the Netherlands.

    4Department of Medical Oncology, Gustave Roussy, Villejuif, France.

    5Department of Pharmacology and Drug Analysis, Gustave Roussy, Villejuif, France.

    6UMR 981, INSERM, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.

    7Department of Pathology, Gustave Roussy, Villejuif, France.

    8Department of Pathology, Cancer Institute, Erasmus MC, Rotterdam, the Netherlands.

    9UMR 1018, INSERM, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.

    10Faculty of Medicine, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin Bicêtre, France.

    11UMR 8203, CNRS, Gustave Roussy, Univ. Paris-Sud, Université Paris-Saclay, Villejuif, France.

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