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Review

Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

1
Pharmacogenomics and Pharmacogenetics Research Unit of the Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
2
Department of Oncology, University of Torino, 10026 Torino, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Academic Editor: Patrizia Limonta
Cancers 2021, 13(12), 2878; https://doi.org/10.3390/cancers13122878
Received: 25 May 2021 / Accepted: 5 June 2021 / Published: 9 June 2021
Despite the adoption of aggressive, multimodal treatment schedules, the cure rate of high-grade osteosarcoma (HGOS) has not significantly improved in the last 30 years. The most relevant problem preventing improvement in HGOS prognosis is drug resistance. Therefore, validated novel biomarkers that help to identify those patients who could benefit from innovative treatment options and the development of drugs enabling personalized therapeutic protocols are necessary. The aim of this review was to give an overview on the most relevant emerging drug resistance-related biomarkers, therapeutic targets and new agents or novel candidate treatment strategies, which have been highlighted and suggested for HGOS to improve the success rate of clinical trials.
High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed. View Full-Text
Keywords: osteosarcoma; drug resistance; personalized medicine; biomarker osteosarcoma; drug resistance; personalized medicine; biomarker
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MDPI and ACS Style

Hattinger, C.M.; Patrizio, M.P.; Fantoni, L.; Casotti, C.; Riganti, C.; Serra, M. Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies. Cancers 2021, 13, 2878. https://doi.org/10.3390/cancers13122878

AMA Style

Hattinger CM, Patrizio MP, Fantoni L, Casotti C, Riganti C, Serra M. Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies. Cancers. 2021; 13(12):2878. https://doi.org/10.3390/cancers13122878

Chicago/Turabian Style

Hattinger, Claudia Maria, Maria Pia Patrizio, Leonardo Fantoni, Chiara Casotti, Chiara Riganti, and Massimo Serra. 2021. "Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies" Cancers 13, no. 12: 2878. https://doi.org/10.3390/cancers13122878

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