title: Significant response after treatment with the mTOR inhibitor sirolimus in combination with carboplatin and paclitaxel in metastatic melanoma patients.
abstract: Melanoma is highly resistant to chemotherapy. In melanoma, the PI3K-AKT-mTOR signaling pathway is constitutively activated through multiple mechanisms. Several experimental studies suggest that targeting the PI3K-AKT-mTOR signaling pathway is a promising strategy to overcome chemoresistance. This is the first report describing a chemosensitizing effect of mTOR inhibition in patients with melanoma. We report two cases of patients with metastatic melanoma who showed significant remission after combination of carboplatin and paclitaxel with the mTOR inhibitor sirolimus. Our case report, together with the literature discussed, suggests that mTOR inhibition possibly enhances the sensitivity of melanoma cells to chemotherapy and should prompt in-depth and clinical investigation.
authors.affiliation: Division of Dermatologic Oncology, Department of Dermatology, University of Tuebingen, Liebermeisterstr. 25, Tübingen D-72076, Germany. friedegund.meier@med.uni-tuebingen.de
authors.forename: Friedegund
authors.initials: F
authors.lastname: Meier
authors.forename: Emmanuella
authors.initials: E
authors.lastname: Guenova
authors.forename: Stephan
authors.initials: S
authors.lastname: Clasen
authors.forename: Thomas
authors.initials: T
authors.lastname: Eigentler
authors.forename: Andrea
authors.initials: A
authors.lastname: Forschner
authors.forename: Ulrike
authors.initials: U
authors.lastname: Leiter
authors.forename: Christina
authors.initials: C
authors.lastname: Zielinski
authors.forename: Björn
authors.initials: B
authors.lastname: Knaudt
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.forename: Mark
authors.initials: M
authors.lastname: Berneburg
mesh_terms: D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy*; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage*; D011494:Protein Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy; D058570:TOR Serine-Threonine Kinases
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D017239:Paclitaxel; D020123:Sirolimus