Molecular Biology of Osteosarcoma

Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond–Blackfan anemia. TP53 is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK–ERK pathways. Several genomic studies showed frequent alterations in the RB gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future.

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Systematic Review of Recurrent Osteosarcoma Systemic Therapy

Cancers ◽

10.3390/cancers13081757 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1757

Author(s):

Ioanna Gazouli ◽

Anastasios Kyriazoglou ◽

Ioannis Kotsantis ◽

Maria Anastasiou ◽

Anastasios Pantazopoulos ◽

...

Keyword(s):

Clinical Evidence ◽

Treatment Effectiveness ◽

Treatment Strategies ◽

Bone Cancer ◽

Predictive Biomarkers ◽

Mtor Inhibitors ◽

Cytotoxic Chemotherapy ◽

Driver Mutations ◽

Preclinical Research ◽

Primary Bone

Osteosarcoma is the most frequent primary bone cancer, mainly affecting those of young ages. Although surgery combined with cytotoxic chemotherapy has significantly increased the chances of cure, recurrent and refractory disease still impose a tough therapeutic challenge. We performed a systematic literature review of the available clinical evidence, regarding treatment of recurrent and/or refractory osteosarcoma over the last two decades. Among the 72 eligible studies, there were 56 prospective clinical trials, primarily multicentric, single arm, phase I or II and non-randomized. Evaluated treatment strategies included cytotoxic chemotherapy, tyrosine kinase and mTOR inhibitors and other targeted agents, as well as immunotherapy and combinatorial approaches. Unfortunately, most treatments have failed to induce objective responses, albeit some of them may sustain disease control. No driver mutations have been recognized, to serve as effective treatment targets, and predictive biomarkers of potential treatment effectiveness are lacking. Hopefully, ongoing and future clinical and preclinical research will unlock the underlying biologic mechanisms of recurrent and refractory osteosarcoma, expanding the therapeutic choices available to pre-treated osteosarcoma patients.

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Parosteal Osteosarcoma with Pancreatic Metastasis and Multiple Relapses: A Case Report and Review of the Literature

Case Reports in Oncology ◽

10.1159/000516033 ◽

2021 ◽

pp. 983-988

Author(s):

Daniel Cirotski ◽

Jyoti Panicker

Keyword(s):

Age Groups ◽

Bone Cancer ◽

Pancreatic Metastasis ◽

Low Grade ◽

Parosteal Osteosarcoma ◽

Disease Course ◽

Review Of The Literature ◽

Histologic Subtype ◽

Primary Bone ◽

Multiple Relapses

Osteosarcoma is the most common primary bone cancer in all age groups. Metastasis mostly occurs with high-grade tumors disseminating to the lungs and other bones. Spread to the pancreas is rare and undocumented in the low-grade subtypes. Additionally, it is uncommon for the disease course of low-grade subtypes to involve multiple relapses. We present a 35-year-old woman with parosteal osteosarcoma who has experienced an atypical metastasis to the pancreas as well as multiple local and pulmonary relapses. The lesion was identified incidentally on routine imaging, and the patient underwent resection. We compare our case to the other reports of pancreatic metastasis in the literature. Despite being especially rare, clinicians ought to be aware of pancreatic metastasis of osteosarcoma. Furthermore, despite parosteal osteosarcoma’s less aggressive disease course, it can uncommonly lead to multiple relapses. We present a rare case exemplifying these phenomena in the prognostically favorable histologic subtype of parosteal osteosarcoma.

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Osteosarcoma and Metastasis Associated Bone Degradation—A Tale of Osteoclast and Malignant Cell Cooperativity

International Journal of Molecular Sciences ◽

10.3390/ijms22136865 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6865

Author(s):

Kirstine Sandal Nørregaard ◽

Henrik Jessen Jürgensen ◽

Henrik Gårdsvoll ◽

Lars Henning Engelholm ◽

Niels Behrendt ◽

...

Keyword(s):

Bone Metastasis ◽

Cancer Cells ◽

Bone Cancer ◽

Degradation Process ◽

Cell Types ◽

Malignant Cell ◽

Pathological Process ◽

Course Of Disease ◽

Bone Degradation ◽

Primary Bone

Cancer-induced bone degradation is part of the pathological process associated with both primary bone cancers, such as osteosarcoma, and bone metastases originating from, e.g., breast, prostate, and colon carcinomas. Typically, this includes a cancer-dependent hijacking of processes also occurring during physiological bone remodeling, including osteoclast-mediated disruption of the inorganic bone component and collagenolysis. Extensive research has revealed the significance of osteoclast-mediated bone resorption throughout the course of disease for both primary and secondary bone cancer. Nevertheless, cancer cells representing both primary bone cancer and bone metastasis have also been implicated directly in bone degradation. We will present and discuss observations on the contribution of osteoclasts and cancer cells in cancer-associated bone degradation and reciprocal modulatory actions between these cells. The focus of this review is osteosarcoma, but we will also include relevant observations from studies of bone metastasis. Additionally, we propose a model for cancer-associated bone degradation that involves a collaboration between osteoclasts and cancer cells and in which both cell types may directly participate in the degradation process.

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Osteosarcoma of the hard palate in a dog ˗ case report

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/1678-4162-12085 ◽

2021 ◽

Vol 73 (1) ◽

pp. 207-213

Author(s):

B.L. Silveira ◽

G.D. Cassali ◽

T.C.M. Lopes

Keyword(s):

Computed Tomography ◽

Hard Palate ◽

Bone Cancer ◽

Metronomic Chemotherapy ◽

Surgical Excision ◽

Well Being ◽

Conventional Chemotherapy ◽

Primary Bone ◽

Firm Mass

ABSTRACT The osteosarcoma (OSA) is the most diagnosed primary bone cancer in canine patients. This work reports a case of a canine, six years old, mongrel, female, intact, with an OSA in the hard palate. Physical examination detected a firm mass in the palate. Thoracic radiographs, hematological and biochemical exams, histopathological exams and computed tomography were requested. A chondroblastic OSA was diagnosed and the tumor was characterized by immunohistochemistry. There was never evidence of metastasis in this case. The treatment consisted of the combination of conventional chemotherapy, metronomic chemotherapy, and palliative care, aiming at greater survival and well-being of the patient since surgical excision was not possible due to the location and extension of the tumor. Osteogenic sarcomas of the hard palate are rarely seen and described in the literature. In this article we present a characterization of the osteosarcoma with uncommon localization in the hard palate.

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Primary bone cancer

Nursing Standard ◽

10.7748/ns2013.11.28.12.22.s27 ◽

2013 ◽

Vol 28 (12) ◽

pp. 22-22

Keyword(s):

Bone Cancer ◽

Primary Bone

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Socio-economic patterning in early mortality of patients aged 0–49 years diagnosed with primary bone cancer in Great Britain, 1985–2008

Cancer Epidemiology ◽

10.1016/j.canep.2018.01.012 ◽

2018 ◽

Vol 53 ◽

pp. 49-55 ◽

Cited By ~ 4

Author(s):

Karen Blakey ◽

Richard G. Feltbower ◽

Peter W. James ◽

Gillian Libby ◽

Charles Stiller ◽

...

Keyword(s):

Great Britain ◽

Bone Cancer ◽

Early Mortality ◽

Primary Bone

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Effectiveness of advanced nursing care (ANC) on bone cancer pain, psychological disorders and quality of life in patients with primary bone cancers: protocol for a PRISMA-compliant meta-analysis

10.37766/inplasy2020.9.0037 ◽

2020 ◽

Author(s):

Lekun Li ◽

Yujie Liu ◽

Xiaofeng Ren ◽

Kai Qu ◽

Xiaona Liu

Keyword(s):

Quality Of Life ◽

Cancer Pain ◽

Nursing Care ◽

Meta Analysis ◽

Bone Cancer ◽

Psychological Disorders ◽

Bone Cancer Pain ◽

Primary Bone

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Massive chondrogenic osteosarcoma of the maxilla: A case report

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v10i1.7322 ◽

1970 ◽

Vol 10 (1) ◽

pp. 57-59

Author(s):

M Irfan ◽

RR Ramli ◽

AK Shamim ◽

A Pohchi

Keyword(s):

Case Report ◽

Surgical Treatment ◽

Oral Cavity ◽

Head And Neck ◽

Hard Palate ◽

Medical Science ◽

Bone Cancer ◽

Wide Margin ◽

Primary Bone

Although osteosarcoma is the most common primary bone cancer, the incidence in head and neck bony structures is extremely low. As the surgical treatment requires a wide margin excision, the operation usually will be very challenging especially if it involves midline structures. We report a case of a young gentleman who had a bony growth over the epicenter of the hard palate which rapidly occupies the whole oral cavity within 6 months duration. The outline of management is discussed. Keywords: Osteosarcoma; hard palate. DOI: 10.3329/bjms.v10i1.7322 Bangladesh Journal of Medical Science Vol.10 No.1 Jan 2010 pp.57-59

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Gene Prioritization through Consensus Strategy, Enrichment Methodologies Analysis, and Networking for Osteosarcoma Pathogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms21031053 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1053 ◽

Cited By ~ 4

Author(s):

Alejandro Cabrera-Andrade ◽

Andrés López-Cortés ◽

Gabriela Jaramillo-Koupermann ◽

César Paz-y-Miño ◽

Yunierkis Pérez-Castillo ◽

...

Keyword(s):

Molecular Mechanisms ◽

Bone Cancer ◽

Interaction Network ◽

Enrichment Analysis ◽

Protein Protein Interaction ◽

Pathogenic Genes ◽

Total List ◽

Consensus Strategy ◽

Primary Bone ◽

Molecular Etiology

Osteosarcoma is the most common subtype of primary bone cancer, affecting mostly adolescents. In recent years, several studies have focused on elucidating the molecular mechanisms of this sarcoma; however, its molecular etiology has still not been determined with precision. Therefore, we applied a consensus strategy with the use of several bioinformatics tools to prioritize genes involved in its pathogenesis. Subsequently, we assessed the physical interactions of the previously selected genes and applied a communality analysis to this protein–protein interaction network. The consensus strategy prioritized a total list of 553 genes. Our enrichment analysis validates several studies that describe the signaling pathways PI3K/AKT and MAPK/ERK as pathogenic. The gene ontology described TP53 as a principal signal transducer that chiefly mediates processes associated with cell cycle and DNA damage response It is interesting to note that the communality analysis clusters several members involved in metastasis events, such as MMP2 and MMP9, and genes associated with DNA repair complexes, like ATM, ATR, CHEK1, and RAD51. In this study, we have identified well-known pathogenic genes for osteosarcoma and prioritized genes that need to be further explored.

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