Figure 1.

Known osteosarcoma biology. Our current understanding defines osteosarcoma in terms of the involvement of particular pathways in specific malignancy-associated processes. For some of these, the mechanisms by which these pathways affect those processes is known in detail (such as for p53 loss in sarcomagenesis). For most, however, the mechanisms through which they affect malignancy are known more generally. The degree to which an involved pathway presents opportunity for targeting depends both on the specific process it mediates, the biochemical properties of the pathway, and the stage of development in which it operates. For instance, it might not make sense to target metastatic dissemination if the process has already occurred when patients are diagnosed. Alternatively, tumors may remain addicted to core processes important for sarcomagenesis even after relapse and metastasis, making them attractive targets, but the biochemistry of those pathways may prove difficult to manipulate. Vast opportunities remain within each of these realms to both identify relevant biology and to clarify the role these factors play in the development and progression of osteosarcoma.