Novel targets with potential therapeutic applications in osteosarcoma

Abstract

For patients with osteosarcoma, the development of metastases, often to the lungs, is the most common cause of death. Long-term outcomes for patients who present with localized or disseminated disease have largely remained unchanged over the past 20 years. Further improvements in outcome are not likely to come from intensification of cytotoxic chemotherapy; as such, new targets for treatment are needed. A view toward such targets in osteosarcoma may be constructed based on three common clinical features of the disease. These include the origin of osteosarcoma in the bone or primitive mesenchymal cells, the predictable process of metastatic progression characterized by this disease, and the development of metastatic lesions almost exclusively in the lung. It is likely and potentially favorable for some targets to be relevant for more than one process. This review summarizes novel targets under evaluation for the treatment of osteosarcoma based on these three features of the disease.

Osteosarcoma

“…Unfortunately, as discussed earlier, the underlying genetic complexity has complicated efforts to identify driving and causal genetic drivers for metastasis in osteosarcoma despite a number of biologic motifs (i.e., growth factor signaling paths, angiogenic phenotype, and mesenchymal stem cell origin) that are consistently associated with osteosarcoma progression and may be described as metastasis ''virulence'' factors, as recently coined by others. (36,37) The following progression (i.e., virulence) factors in osteosarcoma have been consistently held across several investigative platforms and studies (38) :…”

An orthotopic, postsurgical model of luciferase transfected murine osteosarcoma with spontaneous metastasis

“…Metastasis is the most common cause of death from OS [1][2][3]. For this reason, OS patients typically receive systemic chemotherapy for their disease [3].…”

Cross Talk from Pets to People: Translational Osteosarcoma Treatments

“…Osteosarcoma is no exception and one translational example involves the identifi cation of ezrin as a protein that helps drive the m-TOR pathway of tumor cell growth and is a negative prognostic indicator in both dogs and people (Khanna 2008;Khanna et al 2004). In the spirit of comparative research, several clinical trials in dogs with osteosarcoma are ongoing to assess the feasibility of blocking ezrin function with rapamycin.…”