Recent and Ongoing Research into Metastatic Osteosarcoma Treatments

Abstract

The survival rate for metastatic osteosarcoma has not improved for several decades, since the introduction and refinement of chemotherapy as a treatment in addition to surgery. Over two thirds of metastatic osteosarcoma patients, many of whom are children or adolescents, fail to exhibit durable responses and succumb to their disease. Concerted efforts have been made to increase survival rates through identification of candidate therapies via animal studies and early phase trials of novel treatments, but unfortunately, this work has produced negligible improvements to the survival rate for metastatic osteosarcoma patients. This review summarizes data from clinical trials of metastatic osteosarcoma therapies as well as pre-clinical studies that report efficacy of novel drugs against metastatic osteosarcoma in vivo. Considerations regarding the design of animal studies and clinical trials to improve survival outcomes for metastatic osteosarcoma patients are also discussed.

Origin and Therapies of Osteosarcoma

“…Stimulation of the immune system can also be achieved by synthetic molecules, such as mifamurtide (immune modulator liposomal muramyl tripeptide), which is a synthetic derivative of a peptidoglycan that makes up the plasma membrane of bacillus Calmette–Guerin. In cancer, mifamurtide induces the activation of monocytes and macrophages against tumors via the secretion of IL-6, TNFα and increased anti-tumor activity of infiltrating immune cells [ 166 ]. The addition of mifamurtide showed an increase in event-free life span and overall survival [ 167 , 168 ] but without a significant difference between non metastatic and metastatic patients [ 169 ].…”

Analyzing BMP2, FGFR, and TGF Beta Expressions in High-Grade Osteosarcoma Untreated and Treated Autografts Using Proteomic Analysis

“…The most common malignant tumor that arises from the bone is osteosarcoma (OGS). This is commonly observed in children and the middle-aged population [1]. The histological investigations found that OGS typically arises from the mesenchymal stem cells and spindle cells that characterize osteoid formation [2].…”

“…The histological investigations found that OGS typically arises from the mesenchymal stem cells and spindle cells that characterize osteoid formation [2]. Therefore, curative approaches such as surgery and chemotherapy were employed as treatment options that typically showed unsatisfactory results in patients [1]. The commonly known chemotherapy drugs include Doxorubicin, Methotrexate, Cisplatin, and other combinational drugs that are often accompanied by significant side effects [3,4].…”

“…Moreover, OGS primarily metastasizes to the lungs and liver and spreads to the other major organs [1]. On the other hand, most metastatic patients develop severe pain, and it is often difficult to achieve pain relief, resulting in poor quality of life and losing their organs [5].…”

Curcumol Synergizes with Cisplatin in Osteosarcoma by Inhibiting M2-like Polarization of Tumor-Associated Macrophages

“…Furthermore, the high invasiveness and metastasis of OS is the fundamental reason for its aggressiveness, leading to a significant relapse rate. Patients with OS metastasis, particularly those with lung metastasis, have a five-year survival rate of less than 30% [ 8 , 9 , 10 ]. Consequently, focusing on the novel potent chemotherapy regimens is constantly a hot topic in the field of osteosarcoma therapy and plays a key role.…”