Understanding Micrometastatic Disease and Anoikis Resistance in Ewing Family of Tumors and Osteosarcoma

Abstract

Detection of micrometastatic tumor cells in the bone marrow or peripheral blood of patients with Ewing family of tumors (EFTs) and osteosarcoma has been shown to correlate with poor outcome. Although one of the aims of chemotherapy is eradication of micrometa- static disease, these cells vary phenotypically from pri- mary tumor cells and appear to be more resistant to chemotherapy. As a barrier to metastasis, cells nor- mally undergo a form of cell death termed anoikis after they lose contact with the extracellular matrix or neigh- boring cells. Tumor cells that acquire malignant poten- tial have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site and while traveling through the circulation. Inves- tigating mechanisms of resistance to anoikis, therefore, provides a valuable model to investigate regulation of micrometastatic disease. This review focuses on the cur- rent understanding of the mechanisms involved in me- diating cell survival and resistance to anoikis in EFTs and osteosarcoma and discusses future studies that may help to identify novel therapeutics targeted at micro- metastatic disease.