title: Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations.
abstract: Ewing's sarcoma family of tumours comprises a group of very aggressive diseases that are potentially curable with multimodality treatment. Despite the undoubted success of current treatment, approximately 30% of patients will relapse and ultimately die of disease. The insulin-like growth factor 1 receptor (IGF-1R) has been implicated in the genesis, growth, proliferation, and the development of metastatic disease in Ewing's sarcoma. In addition, IGF1-R has been validated, both in vitro and in vivo, as a potential therapeutic target in Ewing's sarcoma. Phase I studies of IGF-1R monoclonal antibodies reported several radiological and clinical responses in Ewing's sarcoma patients, and initial reports of several Phase II studies suggest that about a fourth of the patients would benefit from IGF-1R monoclonal antibodies as single therapy, with approximately 10% of patients achieving objective responses. Furthermore, these therapies are well tolerated, and thus far severe toxicity has been rare. Other studies assessing IGF-1R monoclonal antibodies in combination with traditional cytotoxics or other targeted therapies are expected. Despite, the initial promising results, not all patients benefit from IGF-1R inhibition, and consequently, there is an urgent need for the identification of predictive markers of response.
authors.affiliation: Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Olmos
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Martins
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.forename: Salma
authors.initials: S
authors.lastname: Alam
authors.forename: Michelle
authors.initials: M
authors.lastname: Scurr
authors.forename: Ian R
authors.initials: IR
authors.lastname: Judson