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Advances in the Biology and Therapy of Bone Tumors
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Advances in the Biology and Therapy of Bone Tumors

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 12587

Special Issue Editor

Prof. Dionysios J Papachristou

E-Mail Website
Guest Editor
1. Unit of Bone and Soft Tissue Studies, Department of Histology and HIstopathology, School of Medicine, University of Patras, 26504 Patras, Greece
2. Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
Interests: bone and soft tissue sarcoma pathology and biology; bone biology; metabolic and degenerative bone diseases; bone marrow adiposity

Special Issue Information

Dear Colleagues,

Bone tumors, both benign and malignant, arise from a common progenitor, the mesenchymal stem cell. The current WHO classification (5th Edition, 2020) involves 58 different bone neoplasms. Benign bone tumors are common. Nonetheless, the true incidence of these neoplasm is unknown, since in many cases they are asymptomatic and thus undetectable. Indeed, it is estimated that non-ossifying fibroma, the most common bone tumor, affects 30–40% of children in an indolent fashion. In sharp contrast, bone malignancies (excluding hematopoietic malignancies) are very rare, with an annual incidence of 0.75 cases per 100.000 population in Europe and USA. Osteosarcomas are the most common primary bone sarcomas in children and young adults, followed by Ewing sarcoma. Chondrosarcomas are the most common primary bone sarcomas in the adult population.

The pathobiology of most bone sarcomas is not well defined. Most bone sarcomas, like osteosarcoma, are characterized by complex karyotypes and intertumoral and intratumoral heterogeneity, and therefore the identification of reliable biomarkers and targeted molecular alterations is a hard task to accomplish.

Unveiling the molecular phenomena that govern the pathogenesis of bone tumors may pave the way toward the development of novel therapeutic agents that will add to the armamentarium against bone sarcomas.

This Special Issue of the International Journal of Molecular Sciences on “Advances in the Biology and Therapy of Bone Tumors”, supervised by Prof. Dr. Dionysios Papachristou (University of Patras, Greece) and assisted by Dr. Anastasios Kyriazoglou （University of Athens, Greece), aims at providing the cutting-edge knowledge in every aspect of most of the distinct subtypes bone tumors.

Topics that will be covered include (but are not limited to):

  • Pathobiology of bone benign and malignant tumors;
  • Genetic and epigenetic characteristics of bone sarcomas;
  • Signal transactions pathways implicated in the pathogenesis of bone sarcomas;
  • Current and future therapeutic strategies against bone tumors;
  • Advances in the therapy of metastatic bone sarcomas;
  • The role of immunotherapy in bone sarcomas;
  • Advances in the diagnosis of bone tumors;
  • Metastatic bone disease.

Prof. Dionysios J Papachristou
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • primary bone tumors
  • bone sarcomas
  • pathology
  • bone sarcoma therapy
  • signal transduction pathways
  • bone sarcoma genetics and epigenetic
  • bone metastasis

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Published Papers (4 papers)

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Review

15 pages, 597 KiB  
Review
MicroRNAs as Prognostic Biomarkers and Therapeutic Targets in Chondrosarcoma
by Palina Skipar, Mritunjoy Dey, Jakub Piątkowski, Dorota Sulejczak, Piotr Rutkowski and Anna M. Czarnecka
Int. J. Mol. Sci. 2024, 25(6), 3176; https://doi.org/10.3390/ijms25063176 - 9 Mar 2024
Cited by 1 | Viewed by 1788
Abstract
Chondrosarcoma, the second most common primary malignant bone tumor, originates from cartilaginous tissue and accounts for almost 20% of all primary bone tumors. The management of chondrosarcoma remains challenging due to its diverse clinical course and prognosis, which can range from benign to [...] Read more.
Chondrosarcoma, the second most common primary malignant bone tumor, originates from cartilaginous tissue and accounts for almost 20% of all primary bone tumors. The management of chondrosarcoma remains challenging due to its diverse clinical course and prognosis, which can range from benign to highly aggressive with a huge risk of metastasis. Emerging research has demonstrated the importance of microRNA (miRNA) dysregulation in the pathogenesis of chondrosarcoma. MiRNAs are small, noncoding RNA molecules that play an essential role in gene expression regulation by targeting specific messenger RNAs (mRNAs) for degradation or translational repression. This article provides an extensive review of current miRNA research in chondrosarcoma, focusing on diagnostic strategies, cell cycle regulation, drug resistance, biomarkers of progression, and stem cell phenotype. We will examine recent studies identifying differentially expressed miRNAs in chondrosarcoma compared to normal cartilage tissue, exploring their potential as diagnostic and prognostic biomarkers. Furthermore, we will discuss the role of miRNAs in regulating cell cycle progression and their potential as therapeutic targets to overcome drug resistance. We will also investigate the prospective utility of miRNAs as biomarkers of progression and their role in modulating the stem cell phenotype of chondrosarcoma cells. This article offers a comprehensive analysis of current miRNA research in chondrosarcoma, focusing on its potential as diagnostic and prognostic biomarkers, therapeutic targets, and regulators of disease progression. By integrating the latest discoveries in this field, we aim to contribute to the development of novel approaches to the prevention, diagnosis, and treatment of chondrosarcoma, ultimately enhancing patient outcomes. Full article
(This article belongs to the Special Issue Advances in the Biology and Therapy of Bone Tumors)
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26 pages, 1477 KiB  
Review
A Rare Skeletal Disorder, Fibrous Dysplasia: A Review of Its Pathogenesis and Therapeutic Prospects
by Ha-Young Kim, Jung-Hee Shim and Chan-Yeong Heo
Int. J. Mol. Sci. 2023, 24(21), 15591; https://doi.org/10.3390/ijms242115591 - 26 Oct 2023
Cited by 8 | Viewed by 3962
Abstract
Fibrous dysplasia (FD) is a rare, non-hereditary skeletal disorder characterized by its chronic course of non-neoplastic fibrous tissue buildup in place of healthy bone. A myriad of factors have been associated with its onset and progression. Perturbation of cell–cell signaling networks and response [...] Read more.
Fibrous dysplasia (FD) is a rare, non-hereditary skeletal disorder characterized by its chronic course of non-neoplastic fibrous tissue buildup in place of healthy bone. A myriad of factors have been associated with its onset and progression. Perturbation of cell–cell signaling networks and response outputs leading to disrupted building blocks, incoherent multi-level organization, and loss of rigid structural motifs in mineralized tissues are factors that have been identified to participate in FD induction. In more recent years, novel insights into the unique biology of FD are transforming our understandings of its pathology, natural discourse of the disease, and treatment prospects. Herein, we built upon existing knowledge with recent findings to review clinical, etiologic, and histological features of FD and discussed known and potential mechanisms underlying FD manifestations. Subsequently, we ended on a note of optimism by highlighting emerging therapeutic approaches aimed at either halting or ameliorating disease progression. Full article
(This article belongs to the Special Issue Advances in the Biology and Therapy of Bone Tumors)
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20 pages, 848 KiB  
Review
Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
by Jeong A Park and Nai-Kong V. Cheung
Int. J. Mol. Sci. 2023, 24(15), 12520; https://doi.org/10.3390/ijms241512520 - 7 Aug 2023
Cited by 6 | Viewed by 3249
Abstract
The cure rate for metastatic or relapsed osteosarcoma has not substantially improved over the past decades despite the exploitation of multimodal treatment approaches, allowing long-term survival in less than 30% of cases. Patients with osteosarcoma often develop resistance to chemotherapeutic agents, where personalized [...] Read more.
The cure rate for metastatic or relapsed osteosarcoma has not substantially improved over the past decades despite the exploitation of multimodal treatment approaches, allowing long-term survival in less than 30% of cases. Patients with osteosarcoma often develop resistance to chemotherapeutic agents, where personalized targeted therapies should offer new hope. T cell immunotherapy as a complementary or alternative treatment modality is advancing rapidly in general, but its potential against osteosarcoma remains largely unexplored. Strategies incorporating immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) modified T cells, and T cell engaging bispecific antibodies (BsAbs) are being explored to tackle relapsed or refractory osteosarcoma. However, osteosarcoma is an inherently heterogeneous tumor, both at the intra- and inter-tumor level, with no identical driver mutations. It has a pro-tumoral microenvironment, where bone cells, stromal cells, neovasculature, suppressive immune cells, and a mineralized extracellular matrix (ECM) combine to derail T cell infiltration and its anti-tumor function. To realize the potential of T cell immunotherapy in osteosarcoma, an integrated approach targeting this complex ecosystem needs smart planning and execution. Herein, we review the current status of T cell immunotherapies for osteosarcoma, summarize the challenges encountered, and explore combination strategies to overcome these hurdles, with the ultimate goal of curing osteosarcoma with less acute and long-term side effects. Full article
(This article belongs to the Special Issue Advances in the Biology and Therapy of Bone Tumors)
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17 pages, 782 KiB  
Review
Epigenetic Abnormalities in Chondrosarcoma
by Michał Bereza, Mateusz Dembiński, Agnieszka E. Zając, Jakub Piątkowski, Monika Dudzisz-Śledź, Piotr Rutkowski and Anna M. Czarnecka
Int. J. Mol. Sci. 2023, 24(5), 4539; https://doi.org/10.3390/ijms24054539 - 25 Feb 2023
Cited by 4 | Viewed by 2720
Abstract
In recent years, our understanding of the epigenetic mechanisms involved in tumor pathology has improved greatly. DNA and histone modifications, such as methylation, demethylation, acetylation, and deacetylation, can lead to the up-regulation of oncogenic genes, as well as the suppression of tumor suppressor [...] Read more.
In recent years, our understanding of the epigenetic mechanisms involved in tumor pathology has improved greatly. DNA and histone modifications, such as methylation, demethylation, acetylation, and deacetylation, can lead to the up-regulation of oncogenic genes, as well as the suppression of tumor suppressor genes. Gene expression can also be modified on a post-transcriptional level by microRNAs that contribute to carcinogenesis. The role of these modifications has been already described in many tumors, e.g., colorectal, breast, and prostate cancers. These mechanisms have also begun to be investigated in less common tumors, such as sarcomas. Chondrosarcoma (CS) is a rare type of tumor that belongs to sarcomas and is the second most common malignant bone tumor after osteosarcoma. Due to unknown pathogenesis and resistance to chemo- and radiotherapies of these tumors, there is a need to develop new potential therapies against CS. In this review, we summarize current knowledge on the influence of epigenetic alterations in the pathogenesis of CS by discussing potential candidates for future therapies. We also emphasize ongoing clinical trials that use drugs targeting epigenetic modifications in CS treatment. Full article
(This article belongs to the Special Issue Advances in the Biology and Therapy of Bone Tumors)
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