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Judson I.,Sarcoma Unit
Annals of Oncology | Year: 2010

Soft tissue sarcomas are rare cancers but because of their association with characteristic chromosomal translocations and activating mutations they may be particularly susceptible to molecularly targeted therapies. Gastrointestinal stromal tumour (GIST) became the paradigm for targeted therapy in solid tumours owing to the success of imatinib, which has transformed the prognosis in this disease. Translocation-driven tumours have proved harder to target, but the impact of fusion proteins on gene expression is beginning to be understood and may also reveal new targets for therapy, such as insulin-like growth factor 1 receptor, now that effective inhibitors have been discovered. Angiogenesis inhibition also appears to be a promising area for research in sarcomas and many new targets are emerging at the same time as agents capable of investigating them in the clinic are being developed. It is not unrealistic to hope that targeted therapies will play an increasing role in the management of sarcomas in the near future. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. Source

Scurr M.,Sarcoma Unit
Current Treatment Options in Oncology | Year: 2011

Doxorubicin and ifosfamide are the two chemotherapy drugs that have consistently demonstrated activity in "soft tissue sarcoma" (STS). However, STS is not a homogeneous entity but an umbrella term for a diverse group of more than 40 differing subtypes; each with distinct underlying biology, natural history and response to treatments. The accuracy of the histological and in some cases molecular diagnosis is therefore critical to the optimal treatment of these patients. Leiomyosarcomas have been shown to have limited responsiveness to ifosfamide, but both the combination of gemcitabine and docetaxel, and single agent trabectedin have shown considerable activity in this tumour group. Differences in responses to chemotherapy are seen for leiomyosarcomas of different anatomical sites with uterine leiomyosarcoma demonstrating considerable chemo-responsiveness, whereas vascular leiomyosarcomas appearing far less sensitivity. There is considerable variation in the sensitivity of the three main subtypes of liposarcomas, with well-differentiated liposarcomas showing generalised chemo-resistance through to the impressive responses seen anthracyclines and to trabectedin with the myxoid subtype. Angiosarcomas have demonstrated considerable sensitivity to paclitaxel, a drug that has little activity outside of vascular sarcomas, and liposomal doxorubicin appears to have a particular indication in this subtype. Synovial sarcomas appear to have significant sensitivity to ifosfamide, even on re-challenge. On the other hand, there are subtypes that are chemo-resistant, including gastrointestinal stromal tumour, alveolar soft part sarcoma and clear cell sarcoma, and chemotherapy plays no role in their management. Whilst it is obvious that there is a need to find new agents to treat these tumours, there is an imperative to make sure that the studies that evaluate their "efficacy" are designed to determine the efficacy within differing histiotypes through stratification by histological subtype, or enrichment strategies to ensure that "activity" is not diluted by unresponsive or even chemo-resistant tumour types. © Springer Science+Business Media, LLC 2011. Source

Judson I.,Sarcoma Unit
Clinical Cancer Research | Year: 2012

A population pharmacokinetic study of imatinib in patients with gastrointestinal stromal tumor by Eechoute and colleagues has shown a significant increase in drug clearance over the first 3 months of treatment, resulting in a 30% decrease in drug exposure. This finding clearly shows the possibility of pharmacokinetic resistance in this disease. ©2012 AACR. Source

Krikelis D.,University of Ioannina | Judson I.,Sarcoma Unit
Expert Review of Anticancer Therapy | Year: 2010

Soft tissue sarcomas are a diverse group of rare tumors that comprise 1% of all cancers. Few randomized trials of chemotherapy have been performed but there is a clear role for agents such as doxorubicin and ifosfamide in the palliation of advanced disease. There is uncertainty as to whether sequential single-agent treatment is equivalent to combination chemotherapy. For the majority of histological subtypes adjuvant chemotherapy is not of proven value, although there may be situations where it is advantageous. However, there are other subtypes, such as the Ewing's sarcoma family tumors, for which chemotherapy is an essential part of primary management and has definitely improved survival. Apart from Ewing's sarcoma family tumor and rhabdomyosarcoma, there is increasing specialization of chemotherapy according to histological subtype, such as the use of taxanes for angiosarcoma, gemcitabine and docetaxel for leiomyosarcoma, and trabectedin for leiomyosarcoma and liposarcoma, especially the myxoid/round cell variant. Nevertheless, there are serious limitations to existing treatment and novel therapies need to be developed. © 2010 Expert Reviews Ltd. Source

Thway K.,Sarcoma Unit | Fisher C.,Sarcoma Unit
Advances in Anatomic Pathology | Year: 2014

Myoepithelial neoplasms represent a heterogenous group of tumors of which classification is incomplete and evolving. Those of the soft tissues often form genetically distinct subgroups that differ from those arising within salivary glands. Soft-tissue myoepithelial tumors (including mixed tumors that show true glandular or ductal differentiation) exhibit a spectrum of different morphologic patterns, making them difficult to distinguish from a variety of other neoplasms. They have been increasingly shown to harbor genetic fusions involving EWSR1 and partner genes that are not seen in the well-characterized tumor classes involving EWSR1 translocations. We review the spectrum of soft-tissue myoepithelial tumors, discussing recent immunohistochemical and genetic findings and the differential diagnosis. © 2014 by Lippincott Williams & Wilkins. Source

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