Osteosarcoma

Beird, Hannah C.; Bielack, Stefan; Flanagan, Adrienne M.; Gill, Jonathan; Heymann, Dominique; Janeway, Katherine A.; Livingston, J. Andrew; Roberts, Ryan D.; Strauss, Sandra J.; Görlick, Richard

doi:10.1038/s41572-022-00409-y

Cited by 179 publications

(141 citation statements)

References 211 publications

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“…Combination chemotherapy and complete surgical resection of osteosarcoma is key to a cure, but this only applies to localized osteosarcoma and primary metastatic osteosarcoma. Surgery requires removal of all known metastatic deposits [ 17 ], but osteosarcoma patients are prone to lung metastasis. The five-year survival rate for patients with metastatic osteosarcoma remains low, so predicting tumor metastasis and identifying new prognostic biomarkers are essential.…”

Section: Discussionmentioning

confidence: 99%

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

Huang

Sun

Liu

et al. 2023

Cancers

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Background: The defense response is a type of self-protective response of the body that protects it from damage by pathogenic factors. Although these reactions make important contributions to the occurrence and development of tumors, the role they play in osteosarcoma (OS), particularly in the immune microenvironment, remains unpredictable. Methods: This study included the clinical information and transcriptomic data of 84 osteosarcoma samples and the microarray data of 12 mesenchymal stem cell samples and 84 osteosarcoma samples. We obtained 129 differentially expressed genes related to the defense response (DRGs) by taking the intersection of differentially expressed genes with genes involved in the defense response pathway, and prognostic genes were screened using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression and multivariate Cox regression were then used to establish a DRG prognostic signature (DGPS) via the stepwise method. DGPS performance was examined using independent prognostic analysis, survival curves, and receiver operating characteristic (ROC) curves. In addition, the molecular and immune mechanisms of adverse prognosis in high-risk populations identified by DGPS were elucidated. The results were well verified by experiments. Result: BNIP3, PTGIS, and ZYX were identified as the most important DRGs for OS progression (hazard ratios of 2.044, 1.485, and 0.189, respectively). DGPS demonstrated outstanding performance in the prediction of OS prognosis (area under the curve (AUC) values of 0.842 and 0.787 in the training and test sets, respectively, adj-p < 0.05 in the survival curve). DGPS also performed better than a recent clinical prognostic approach with an AUC value of only 0.674 [metastasis], which was certified in the subsequent experimental results. These three genes regulate several key biological processes, including immune receptor activity and T cell activation, and they also reduce the infiltration of some immune cells, such as B cells, CD8+ T cells, and macrophages. Encouragingly, we found that DGPS was associated with sensitivity to chemotherapeutic drugs including JNK Inhibitor VIII, TGX221, MP470, and SB52334. Finally, we verified the effect of BNIP3 on apoptosis, proliferation, and migration of osteosarcoma cells through experiments. Conclusions: This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients.

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Section: Discussionmentioning

confidence: 99%

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

Huang

Sun

Liu

et al. 2023

Cancers

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“…For all these trials, there are only two main types of OS: soft and solid, as observed in the table. The following active pharmaceutical ingredients (API) are appropriate for OS: topotecan (Tpt) [45], pazopanib (Pzp) [46], placebo (Plb) [47], gemcitabine (Gct) [48], M6620 [49][50], regorafenib (Rgf) [51][52], glembatumumab vedotin (GV) [53][54], lenvatinib [55], etoposide and ifosfamide (EnI) [56], nab-rapamycin (Rpm) [57][58], cyclophosphamide (Cfa) [59], simvastatin (Sim) [60], myeloid growth factor (MGF) [61], nab-paclitaxel [62][63], methotrexate (Mtx) [64], and doxorubicin (Dox) [65]. Besides, the primary tests, such as laboratory biomarker analyses [66] and dose escalation studies [67], were conducted for these successful triumphs.…”

Section: Clinical Advancementmentioning

confidence: 99%

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

Zaidi¹,

Haque²,

Miskon³

2023

Preprint

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There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.

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“…Non-invasive imaging through fluorescence dyes attached to nanoparticles can target osteosarcoma and metastasis in mice [ 29 ]. While the primary treatment of osteosarcoma includes surgery, chemotherapy, and radiation, patients require multidisciplinary care; a team of surgeons, oncologists, physical therapists, and psychiatrists, among others, are necessary for the proper multifactorial treatment of osteosarcoma in order to address the patient’s medical and socioeconomic needs [ 30 ]. Despite extensive involvement in patient care and treatment options, outcomes are usually poor for osteosarcoma, and the exploration of novel treatment options is necessary to reduce patient morbidity and mortality.…”

Section: Potential Therapies For Osteosarcomamentioning

confidence: 99%

The Use of Hydrogels for the Treatment of Bone Osteosarcoma via Localized Drug-Delivery and Tissue Regeneration: A Narrative Review

Tharakan

Raja

Pietraru

et al. 2023

Gels

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Osteosarcoma is a malignant tumor of bone that leads to poor mortality and morbidity. Management of this cancer through conventional methods involves invasive treatment options that place patients at an increased risk of adverse events. The use of hydrogels to target osteosarcoma has shown promising results both in vitro and in vivo to eradicate tumor cells while promoting bone regeneration. The loading of hydrogels with chemotherapeutic drugs provides a route for site-specific targeted therapy for osteosarcoma. Current studies demonstrate tumor regression in vivo and lysis of tumor cells in vitro when exposed to doped hydrogel scaffolds. Additionally, novel stimuli-responsive hydrogels are able to react with the tissue microenvironment to facilitate the controlled release of anti-tumor drugs and with biomechanical properties that can be modulated. This narrative review of the current literature discusses both in vitro and in vivo studies of different hydrogels, including stimuli-responsive, designed to treat bone osteosarcoma. Future applications to address patient treatment for this bone cancer are also discussed.

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Osteosarcoma

Cited by 179 publications

References 211 publications

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma

Relationship between Osteosarcoma Therapy and Tumorigenesis, Metastasis, Immune Evasion, and Chemoresistance

The Use of Hydrogels for the Treatment of Bone Osteosarcoma via Localized Drug-Delivery and Tissue Regeneration: A Narrative Review

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