Osteosarcoma: a review of current and future therapeutic approaches

Zhao, Xin; Wu, Qirui; Gong, Xiuqing; Liu, Jinfeng; Ma, Yujie

doi:10.1186/s12938-021-00860-0

Cited by 145 publications

(108 citation statements)

References 99 publications

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“…To avoid using small systemic dose or large local dose of plain chemotherapeutics, nanocarrier systems with controlled drug release can be employed. Particularly, bonetargeted drug delivery systems aim to concentrate drugs in tumor sites, protect drugs from rapid clearance, prolong their circulation times, enhance therapeutic efficacy, and reduce the systemic adverse effects [9,15,88,89].…”

Section: Drug Deliverymentioning

confidence: 99%

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

Bădilă

Rădulescu

Niculescu

et al. 2021

Cancers

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In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, severe side effects, formation of large bone defects), which limit their application and efficacy. In recent years, these procedures were combined with several adjuvant therapies, with different degrees of success. To overcome the drawbacks of current therapies and improve treatment outcomes, other strategies started being investigated, like carrier-mediated drug delivery, bone substitutes for repairing bone defects, and multifunctional scaffolds with bone tissue regeneration and antitumor properties. Thus, this paper aims to present the types of bone tumors and their current treatment approaches, further focusing on the recent advances in new therapeutic alternatives.

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Section: Drug Deliverymentioning

confidence: 99%

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

Bădilă

Rădulescu

Niculescu

et al. 2021

Cancers

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“…The development of clinical trials including small molecules that could restore the wild-type conformation of p53 and gene therapy combined with chemotherapy, radiation therapy, or conventional surgery are expected in the future. Despite great progress in gene therapy, it is still most commonly in the experimental stage, not in the actual clinical application except for Gendicine, approved in China [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

TP53 in Biology and Treatment of Osteosarcoma

Synoradzki

Bartnik

Czarnecka

et al. 2021

Cancers

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The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate which are more common and describe their role in in vitro and animal models. We also describe animal models with TP53 dysfunction, which provide a good platform for testing the potential therapeutic approaches. Finally, we have indicated a whole range of pharmacological compounds that modulate the action of p53, stabilize its mutated versions or lead to its degradation, cause silencing or, on the contrary, induce the expression of its functional version in genetic therapy. Although many of the described therapies are at the preclinical testing stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future.

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“…Whereas 5-year overall survival is around 50–80% in patients with localized osteosarcoma [ 1 ], only 27% of patients with metastatic disease survive longer than 5 years [ 3 ]. No agents exist that can successfully cure metastatic osteosarcoma, so it is essential that such treatment is developed [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis

Tsai

Lai

Hsu

et al. 2021

IJMS

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Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvβ3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and β3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvβ3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvβ3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvβ3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.

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Osteosarcoma: a review of current and future therapeutic approaches

Cited by 145 publications

References 99 publications

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

TP53 in Biology and Treatment of Osteosarcoma

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis

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