S Scheipl1, B Liegl-Atzwanger2, J Szkandera3, B Rinner4, C Viertler2, J Friesenbichler5, M Bergovec5, A Leithner5. 1. Univ.-Klinik für Orthopädie und Traumatologie, Medizinische Universität Graz, Auenbruggerplatz 5, 8036, Graz, Österreich. susanne.scheipl@medunigraz.at. 2. Diagnostik- und Forschungsinstitut für Pathologie, Medizinische Universität Graz, Neue Stiftingtalstraße 6, 8010, Graz, Österreich. 3. Univ.-Klinik für Innere Medizin, Klin. Abt. für Onkologie, Medizinische Universität Graz, Auenbruggerplatz 15, 8036, Graz, Österreich. 4. Biomedizinische Forschung, Medizinische Universität Graz, Roseggerweg 48, 8036, Graz, Österreich. 5. Univ.-Klinik für Orthopädie und Traumatologie, Medizinische Universität Graz, Auenbruggerplatz 5, 8036, Graz, Österreich.
Abstract
BACKGROUND: Personalised tumour therapies aim to selectively target pathways and structures to which a tumour shows an oncogenic addiction. OBJECTIVE AND METHOD: This article aims to provide an overview of relevant genetic alterations in bone and soft-tissue tumours, which might serve as potential therapeutic targets for personalised medicines in the future. Recent approaches towards a personalised treatment of various tumours of bone and soft tissues are reviewed. RESULTS: Molecular diagnosis has become an essential tool for the characterisation of bone and soft-tissue tumours. Currently, no targeted therapies are routinely available for bone sarcomas. Denosumab is merely a symptomatic treatment for giant cell tumours of the bone. Imatinib has become the paradigm of a targeted treatment for subgroups of malignant gastrointestinal stromal tumours (GISTs) and dermatofibrosarcoma protuberans. Antiangiogenic multikinase inhibitors, various other tyrosine kinase inhibitors (TKIs) and monoclonal antibodies are currently being evaluated in several (sub-)types of soft-tissue sarcomas. Sorafenib showed promising results in the treatment of aggressive desmoid-type fibromatosis. Histology-tailored chemotherapies did not yield superior results in a prospective randomised multicentre trial. CONCLUSION: More in-depth knowledge is required for many sarcomas to link their genetic alterations to tumorigenesis in order to develop efficient personalised treatment strategies. Clinical trial designs need to be adapted to evaluate new therapeutic strategies in these ultra-rare tumours and their various sub-types more efficaciously.
BACKGROUND: Personalised tumour therapies aim to selectively target pathways and structures to which a tumour shows an oncogenic addiction. OBJECTIVE AND METHOD: This article aims to provide an overview of relevant genetic alterations in bone and soft-tissue tumours, which might serve as potential therapeutic targets for personalised medicines in the future. Recent approaches towards a personalised treatment of various tumours of bone and soft tissues are reviewed. RESULTS: Molecular diagnosis has become an essential tool for the characterisation of bone and soft-tissue tumours. Currently, no targeted therapies are routinely available for bone sarcomas. Denosumab is merely a symptomatic treatment for giant cell tumours of the bone. Imatinib has become the paradigm of a targeted treatment for subgroups of malignant gastrointestinal stromal tumours (GISTs) and dermatofibrosarcoma protuberans. Antiangiogenic multikinase inhibitors, various other tyrosine kinase inhibitors (TKIs) and monoclonal antibodies are currently being evaluated in several (sub-)types of soft-tissue sarcomas. Sorafenib showed promising results in the treatment of aggressive desmoid-type fibromatosis. Histology-tailored chemotherapies did not yield superior results in a prospective randomised multicentre trial. CONCLUSION: More in-depth knowledge is required for many sarcomas to link their genetic alterations to tumorigenesis in order to develop efficient personalised treatment strategies. Clinical trial designs need to be adapted to evaluate new therapeutic strategies in these ultra-rare tumours and their various sub-types more efficaciously.
Authors: Christopher R Heery; B Harpreet Singh; Myrna Rauckhorst; Jennifer L Marté; Renee N Donahue; Italia Grenga; Timothy C Rodell; William Dahut; Philip M Arlen; Ravi A Madan; Jeffrey Schlom; James L Gulley Journal: Cancer Immunol Res Date: 2015-06-30 Impact factor: 11.151
Authors: M Agulnik; J L Yarber; S H Okuno; M von Mehren; B D Jovanovic; B E Brockstein; A M Evens; R S Benjamin Journal: Ann Oncol Date: 2012-08-21 Impact factor: 32.976
Authors: Sam Behjati; Patrick S Tarpey; Nadège Presneau; Susanne Scheipl; Nischalan Pillay; Peter Van Loo; David C Wedge; Susanna L Cooke; Gunes Gundem; Helen Davies; Serena Nik-Zainal; Sancha Martin; Stuart McLaren; Victoria Goodie; Ben Robinson; Adam Butler; Jon W Teague; Dina Halai; Bhavisha Khatri; Ola Myklebost; Daniel Baumhoer; Gernot Jundt; Rifat Hamoudi; Roberto Tirabosco; M Fernanda Amary; P Andrew Futreal; Michael R Stratton; Peter J Campbell; Adrienne M Flanagan Journal: Nat Genet Date: 2013-10-27 Impact factor: 38.330
Authors: Monika Toporkiewicz; Justyna Meissner; Lucyna Matusewicz; Aleksander Czogalla; Aleksander F Sikorski Journal: Int J Nanomedicine Date: 2015-02-17