摘要
Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens.Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets.Defects in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes.As such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies.Born out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical testing.They broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing agents.As new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than ever.In this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.
Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens.Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets.Defects in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes.As such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies.Born out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical testing.They broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing agents.As new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than ever.In this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.
基金
supported in part by research grants from the National Institutes of Health(AT004418,AR50142,AR054381 to TCH,RCH and HHL)
the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH)
