title: Infrared spectra of primary melanomas can predict response to chemotherapy: The example of dacarbazine.
abstract: Metastatic melanomas are highly aggressive and median survival is 6-9months for stage IV patients in the absence of treatment with anti-tumor activity. Dacarbazine is an alkylating agent that has been widely used in the treatment of metastatic melanomas and that could be still used in combination with targeted or immune therapies. Indeed, therapeutic benefits of these treatments in monotherapy are poor and one option to improve them is to combine drugs and/or to better anticipate the individual response to a defined treatment. To our best knowledge and to date, there is no test available to predict the response of a patient to dacarbazine. We show here that examination of melanoma histological sections by infrared micro-spectroscopy reveals the sensitivity of the cancer to dacarbazine. Unsupervised analysis of the FTIR spectra evidences spontaneous and significant clustering of infrared spectra into two groups that match the clinical responsiveness of the patients to dacarbazine used as a first-line treatment. A supervised model resulted in 83% of the patient status (responder/non-responder) being correctly identified. The spectra revealed a key modification in the nature and quantity of lipids in the cells of both groups.
authors.affiliation: Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: noemwald@ulb.ac.be.
authors.forename: N
authors.initials: N
authors.lastname: Wald
authors.affiliation: Department of Dermatology, Angers University Hospital, Angers, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Le Corre
authors.affiliation: Department of Dermatology, Angers University Hospital, Angers, France.
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.affiliation: Laboratoire de Cancérologie et Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Mathieu
authors.affiliation: Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Goormaghtigh
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003606:Dacarbazine / Q000627:therapeutic use*; D006801:Humans; D008545:Melanoma / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy* / Q000473:pathology; D008954:Models, Biological; D025341:Principal Component Analysis; D011379:Prognosis; D012372:ROC Curve; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine
keywords: Dacarbazine; FTIR imaging; FTIR spectroscopy; Melanoma; Metastases; Prediction; Response rate