Sarcomas remain a extremely challenging malignancy to treat clinically, and metastatic spread remains the single most powerful predictor of poor outcome in sarcoma patients. Despite occurring throughout the life spectrum, these tumours are proportionally more common in paediatric compared to adult age groups, as they account for up to 20% of all paediatric malignancies. Modern multi-agent chemotherapy regimens have made tremendous improvements to the outcomes of patients with localized high-risk childhood sarcomas such as Ewing sarcoma (ES), rhabdomyosarcoma (RMS), and osteosarcoma (OS). However, the prognosis for patients with metastatic disease remains dismal.Therefore a better understanding of the signalling pathways that impact metastatic spread has tremendous potential to reduce disease burden in childhood sarcoma. In my current research project, we are attempting a novel and different strategy, which is to target a highly conserved acute adaptive mechanism which we believe is a common Achilles heel of tumor cells, namely stress granule (SG) formation. Our previous work highlights the critical role of stress granules in sarcoma progression. Moreover, a pilot study performed by our group showed that targeting SGs with a single class of SG inhibitors in childhood sarcoma cell xenografts blocks their metastatic capacity in vivo. Similar effects were observed when prostate carcinoma cell line xenografts were targeted in vivo with the same inhibitor. The current study will be directed to establish a high-throughput cell-based assay for large-scale screening of broader classes of pharmacologically active compounds to identify and characterize novel SG inhibitors as inducers, which we postulate will lead to exciting new treatment strategies for childhood cancers, and potentially other tumour types.