Molecular pathogenesis and therapeutic strategies of human osteosarcoma

Abstract

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 locallywhile 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.

Resveratrol eliminates cancer stem cells of osteosarcoma by STAT3 pathway inhibition

“…Osteosarcoma is the most common type of bone cancer and the second leading cause of cancer-related deaths in children and adolescents, which shows an incidence of 3.4 cases per million people every year worldwide. [ 1 ]. Combination of surgery and adjacent chemotherapy is still the conventional therapeutic regimens for osteosarcoma patients [ 2 ].…”

p38γ overexpression promotes osteosarcoma cell progression

“…OS, often detected in children and young adults, is a genetically complex disease [ 6 , 13 , 14 ]. Genomic instability is a major contributor to OS disease progression and is associated with a poor prognosis [ 6 , 13 , 14 ]. The underlying molecular mechanisms of OS are still poorly understood [ 6 , 13 , 14 ].…”

“…Genomic instability is a major contributor to OS disease progression and is associated with a poor prognosis [ 6 , 13 , 14 ]. The underlying molecular mechanisms of OS are still poorly understood [ 6 , 13 , 14 ]. The function of p38γ, an alternative p38 MAPK, has been disregarded in the studies and remains largely unknown [ 15 ].…”

The therapeutic value of the SphK1-targeting microRNA-3677 in human osteosarcoma cells

“…Osteosarcoma (OS) is a common malignant bone tumor [1,2]. Each year it is estimated that over three million new cases of OS will be diagnosed, mostly in children and adolescents [1,2].…”

“…Each year it is estimated that over three million new cases of OS will be diagnosed, mostly in children and adolescents [1,2]. OS survival has been significantly improved over the past decades, owing to progress in the early disease diagnosis techniques and latest developments in molecularly-targeted and/or combination therapies [1,2]. For the recurrent and metastatic OS, the current clinical therapies are limited [1,2].…”