Progress in the treatment of
Ewing's sarcoma, the second most common bone tumour in children and adolescents, has improved survival from about 10% in the period before
chemotherapy was introduced to about 75% today for patients with localised tumours. However, patients with
metastases still fare badly, and the
therapy carries short-term and long-term toxicities. Multidisciplinary care is indispensable for these patients. Molecular techniques and new imaging modalities are affecting the diagnosis and classification of patients with
Ewing's sarcoma. Cooperative group studies have led to
chemotherapy regimens using the same drugs (
vincristine,
doxorubicin,
cyclophosphamide,
ifosfamide, and
etoposide), although the exact regimens differ in Europe and North America. The EWS-ETS family of gene fusions and their downstream effects in Ewing's
sarcomas provide opportunities for new approaches to treatment. These include the inhibition of the fusion gene or its
protein product, and pathways related to IGF1 and mTOR. Inhibition of
tyrosine kinases, exploitation of non-apoptotic cell death, and interference with angiogenesis are promising new approaches. With many new approaches and relatively few patients, it will be challenging to integrate new and established treatments through clinical trials.