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Review
. 2021 Mar 12;10(6):1182.
doi: 10.3390/jcm10061182.

Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies

Richa Rathore  1 , Brian A Van Tine  1   2   3
Affiliations
Review

Pathogenesis and Current Treatment of Osteosarcoma: Perspectives for Future Therapies

Richa Rathore et al. J Clin Med. .

Abstract

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. The standard-of-care curative treatment for osteosarcoma utilizes doxorubicin, cisplatin, and high-dose methotrexate, a standard that has not changed in more than 40 years. The development of patient-specific therapies requires an in-depth understanding of the unique genetics and biology of the tumor. Here, we discuss the role of normal bone biology in osteosarcomagenesis, highlighting the factors that drive normal osteoblast production, as well as abnormal osteosarcoma development. We then describe the pathology and current standard of care of osteosarcoma. Given the complex heterogeneity of osteosarcoma tumors, we explore the development of novel therapeutics for osteosarcoma that encompass a series of molecular targets. This analysis of pathogenic mechanisms will shed light on promising avenues for future therapeutic research in osteosarcoma.

Keywords: mesenchymal stem cell; methotrexate; osteoblast; osteosarcoma; sarcoma.

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Conflict of interest statement

R.R. declares no conflicts of interest. B.A.V.T. declares Basic Science Grant funding from Pfizer, TRACON Pharmaceuticals, and Merck; consulting fees from Epizyme, Eli Lilly, CytRX, Janssen Pharmaceutica, Immune Design, Daiichi Sankyo, Plexxikon, Deciphera Pharmaceuticals, and Adaptimmune; travel support from GlaxoSmithKline; is an unpaid advisor to Advenchen Laboratories; and is on the Scientific Advisory Board of Polaris Inc. The funders had no role in the design of the study; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Mesenchymal stem cells differentiate into various cell types based on the expression of different transcription factors and protein families, highlighted in gray. Sox9: SRY-box transcription factor 9; Runx2: Runt-related transcription factor 2; Sp7: osterix; BMP: bone morphogenic protein; Wnt: wingless and int-1; PPARγ: peroxisome proliferator-activated receptor gamma; TGFβ: transforming growth factor-beta.
Figure 2
Figure 2
Overexpression of certain transcription factors and oncogenes and dysregulation of tumor suppressor genes can drive osteosarcoma development. TP53: tumor protein p53; Rb: retinoblastoma; Runx2: Runt-related transcription factor 2; ALP: alkaline phosphatase; Gli1: glioma-associated oncogene homolog 1; Sox9: SRY-box transcription factor 9; Sp7: osterix; BMP: bone morphogenic protein; Wnt: wingless and int-1; TGFβ: transforming growth factor-beta; SMAD4: Mothers against decapentaplegic homolog 4; MMP: matrix metalloproteinase; NF2: neurofibromatosis-2; RANKL: receptor activator of nuclear-factor kappa B ligand.
See this image and copyright information in PMC

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