Autophagy in osteosarcoma.

Osteosarcoma (OS) metastatic disease is resistant to conventional chemotherapy. Tumor resistance to chemotherapy has been one of the major areas of concern to clinicians and the topic of many laboratory investigators. Evaluation of mechanisms implicated in OS lung metastasis resistance to chemotherapy has been the focus of some of our most recent work. We have previously demonstrated the therapeutic efficacy of aerosol gemcitabine (GCB) in OS lung metastases. However, a subset of cells fails to respond to GCB treatment and persists as isolated lung metastases in vivo. Autophagy, a physiological mechanism that supports nutritional deprivation under stressful conditions, has been implicated in tumor resistance to chemotherapy. We demonstrated the induction of autophagy by GCB in LM7 metastatic human OS cells and K7M3 metastatic murine OS cells. Inhibition of autophagy resulted in increased sensitivity to GCB in LM7 cells. By contrast, inhibiting autophagy in K7M3 cells decreased GCB sensitivity. Defining the role autophagy plays in chemotherapy response in different tumor types has become of greater importance in order to identify the best suitable therapeutic approach. In this chapter, we summarize some of the most recent work related to autophagy in OS, identify some of the known mechanisms, and address the different roles autophagy plays in chemotherapy response.