Osteosarcoma: Cells‐of‐Origin, Cancer Stem Cells, and Targeted Therapies

Abstract

Osteosarcoma (OS) is the most common type of primary solid tumor that develops in bone. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for those patients with metastatic or recurrent OS remains dismally poor and, therefore, novel agents and treatment regimens are urgently required. A hypothesis to explain the resistance of OS to chemotherapy is the existence of drug resistant CSCs with progenitor properties that are responsible of tumor relapses and metastasis. These subpopulations of CSCs commonly emerge during tumor evolution from the cell-of-origin, which are the normal cells that acquire the first cancer-promoting mutations to initiate tumor formation. In OS, several cell types along the osteogenic lineage have been proposed as cell-of-origin. Both the cell-of-origin and their derived CSC subpopulations are highly influenced by environmental and epigenetic factors and, therefore, targeting the OS-CSC environment and niche is the rationale for many recently postulated therapies. Likewise, some strategies for targeting CSC-associated signaling pathways have already been tested in both preclinical and clinical settings. This review recapitulates current OS cell-of-origin models, the properties of the OS-CSC and its niche, and potential new therapies able to target OS-CSCs.

LncRNA GAS5 Represses Osteosarcoma Cells Growth and Metastasis via Sponging MiR-203a

“…Surgery is one of the main treatments for patients with osteosarcoma. Despite the success of surgery for osteosarcoma, the 5-year overall survival rate of patients with metastatic or recurrent osteosarcoma remains dismally poor [2]. This calls for a better understanding of the pathogenesis and molecular mechanisms of osteosarcoma, which will helpful in the clinical treatment and prognosis of this disease.…”

Cancer stem cells in osteosarcoma

“…Osteosarcoma is a vascularized tumour characterized by typical osteoid matrix formed by cancer cells (Figures 1D,E). Evidence comes predominantly from in vivo studies using MSCs and/or osteoprogenitors in which for example mutations in genes such as P53 and RB and/or aberrant Hedgehog and NOTCH signalling were shown to induce osteosarcoma (7)(8)(9). The terminology of 'cancer stem cells' is still under debate with the association to stem cells remaining controversial.…”

Deoxyelephantopin Induces Reactive Oxygen Species-Mediated Apoptosis and Autophagy in Human Osteosarcoma Cells

“…This disease is characterized by the generation of immature osteoid matrix through mesenchymal stem cell-derived tumor cells, which primarily occurs in the distal end of long bones, such as the femur and humerus [2]. The current treatments for osteosarcoma include surgery, chemotherapy and radiotherapy.…”