Research progress on the multidrug resistance mechanisms of osteosarcoma chemotherapy and reversal

Abstract

Osteosarcoma (OS) is the most common and aggressive primary malignant type of bone cancer in children and adolescents. Chemotherapy is one of the most important treatments for OS. Although cancer therapy has improved over the past few decades, survival outcomes for OS patients remain unsatisfactory. One of the primary reasons for the failure of current treatments is that patients with stage IV cancer often develop resistance to anticancer agents. This article will review multidrug resistance (MDR) mechanisms of OS and strategies for overcoming resistance.

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

“…Despite the improved prognosis, resistance to chemotherapy remains an obstacle in the treatment of osteosarcoma [51]. The identification of signals and effective agents that promote cell death may provide clues for developing new therapeutic strategies for chemoresistant osteosarcoma [52, 53]. Effective agents such as natural compounds, miRNA and proteins in treatment of osteosarcoma were summarized.…”

The effective combination therapy against human osteosarcoma: doxorubicin plus curcumin co-encapsulated lipid-coated polymeric nanoparticulate drug delivery system

“…Until now, doxorubicin (DOX), cisplatin and methotrexate are the commonly used chemotherapeutics to treat OS. However, despite advances in surgical techniques and neoadjuvant chemotherapy regimens, the failure of current treatment accounts for about 30%, which is mainly due to drug resistance in patients with stage IV cancer (Desandes, 2007;Li S et al, 2015).…”

“…Multidrug resistance (MDR) in OS therapy due to various mechanisms, including decreased intracellular drug accumulation mediated by P-glycoprotein (P-gp), apoptosis inhibition by Bcl-2 or p53 or miRNAs, up-regulation of nuclear factor kappa B (NF-kB) activity, blocking the binding of chemotherapy drugs DNA Topo II, detoxification in the cell by GSTP1, enhanced DNA repair by ERCC or APE1 and cancer stem cells mediated resistance (Nedelcu et al, 2008;Rajkumar & Yamuna, 2008;Wu et al, 2012;Li S et al, 2015). In order to overcome the resistance mechanism caused by P-gp, recent researches have focused on the novel drug delivery system-lipid based nanoparticles (Susa et al, 2010;Dhule et al, 2012).…”

Targeting protein kinases to reverse multidrug resistance in sarcoma

“…Unfortunately, the efficacy of these agents is often hampered by the development of multidrug resistance (MDR). In osteosarcoma, 30% to 40% of patients will experience MDR associated with recurrence or metastasis despite improved multimodality therapy 3 . A number of patients will also develop resistance to multiple types of chemotherapy after prolonged periods of treatment.…”