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Targeting the Insulin-Like Growth Factor 1 Receptor in Ewing's Sarcoma: Reality and Expectations
David Olmos1, Ana Sofia Martins, Robin L Jones
1Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
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.
Insights
Targeting the insulin-like growth factor 1 receptor (IGF-1R) shows promise for Ewing's sarcoma treatment. While IGF-1R inhibitors are well-tolerated, identifying predictive markers is crucial as not all patients respond.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Ewing's sarcoma is an aggressive cancer with a significant relapse rate.
- The insulin-like growth factor 1 receptor (IGF-1R) plays a key role in Ewing's sarcoma development and progression.
- IGF-1R is a validated therapeutic target in preclinical and clinical studies.
Purpose of the Study:
- To evaluate the efficacy and safety of IGF-1R targeted therapies in Ewing's sarcoma.
- To explore the potential of IGF-1R monoclonal antibodies as a treatment option.
- To highlight the need for predictive markers of response to IGF-1R inhibition.
Main Methods:
- Review of Phase I and Phase II clinical studies involving IGF-1R monoclonal antibodies.
- Analysis of radiological and clinical responses in Ewing's sarcoma patients.
- Assessment of treatment tolerability and toxicity.
Main Results:
- Phase I studies showed radiological and clinical responses.
- Phase II studies suggest approximately 25% of patients benefit from single-agent IGF-1R antibodies, with 10% objective responses.
- IGF-1R targeted therapies demonstrated good tolerability with rare severe toxicity.
Conclusions:
- IGF-1R monoclonal antibodies represent a promising therapeutic strategy for Ewing's sarcoma.
- Further research is needed to identify biomarkers for patient selection.
- Combination therapies involving IGF-1R inhibitors are under investigation.
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