Bone and Soft Tissue Tumors: Molecular Mechanisms, Clinical Practice, and Emerging Therapeutics

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 3122

Special Issue Editors


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Guest Editor
Department of Rehabilitation Science, Graduate School of Health Sciences, Kobe University, Kobe, Japan
Interests: bone and soft tissue sarcoma

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Guest Editor
Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Interests: sarcoma; rare cancer; genomics; clinical trial
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
School of Medicine, Jichi Medical University, Kawachi District, Shimotsuke, Japan
Interests: osteoclast; osteosarcoma; osteochondroma

Special Issue Information

Dear Colleagues,

Malignant bone and soft tissue tumors are defined as a rare cancer. Since the introduction of perioperative chemotherapy combined with wide surgical excision for several sarcomas, including osteosarcoma and Ewing sarcoma, the prognosis of patients with localized disease has improved. In the past decade, molecular-targeted drugs for soft tissue sarcoma have been developed and used clinically. However, life prognosis, especially for the patients with metastatic or recurrent disease, has not improved in recent decades. As such, novel diagnostic and therapeutic approaches are urgently needed. This Special Issue will focus on recent developments in basic and clinical research for malignant bone and soft tissue tumors. Both original research articles and reviews are welcome. Research topics may include the following:

  • Basic research for molecular mechanisms of sarcoma development;
  • Molecular-targeted drugs for bone and soft tissue sarcoma;
  • Prognostic parameters and biomarkers;
  • New imaging modalities;
  • New surgical options for local treatment;
  • The role of ‘omics’ (genomics, transcriptomics, proteomics, and metabolomics).

We look forward to receiving your contributions.

Prof. Dr. Toshihiro Akisue
Dr. Shintaro Iwata
Dr. Toru Akiyama
Guest Editors

Manuscript Submission Information

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Keywords

  • bone and soft tissue sarcoma
  • imaging modality
  • surgical treatment
  • systemic treatment
  • molecular-targeted treatment
  • biomarkers
  • prognostic parameters

Published Papers (3 papers)

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Research

16 pages, 4585 KiB  
Article
Therapeutic Potential of Bromodomain and Extra-Terminal Domain Inhibitors for Synovial Sarcoma Cells
by Yuki Kotani, Yoshinori Imura, Sho Nakai, Ryota Chijimatsu, Haruna Takami, Akitomo Inoue, Hirokazu Mae, Satoshi Takenaka, Hidetatsu Outani and Seiji Okada
Cancers 2024, 16(6), 1125; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16061125 - 11 Mar 2024
Viewed by 732
Abstract
Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established [...] Read more.
Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established role of SS18-SSX in epigenetic regulation, we focused on bromodomain and extra-terminal domain protein (BET) inhibitors and epigenetic agents. Our investigation of the BET inhibitor ABBV-075 revealed its pronounced antitumor effects, inducing G1-phase cell-cycle arrest and apoptosis, in four SS cell lines. Notably, BET inhibitors exhibited regulatory control over crucial cell-cycle regulators, such as MYC, p21, CDK4, and CDK6. Additionally, RNA sequencing findings across the four cell lines revealed the significance of fluctuating BCL2 family protein expression during apoptotic induction. Notably, variations in the expression ratio of the anti-apoptotic factor BCLxL and the pro-apoptotic factor BIM may underlie susceptibility to ABBV-075. Additionally, knockdown of SS18-SSX, which upregulates BCL2, reduced the sensitivity to ABBV-075. These findings suggest the potential utility of BET inhibitors targeting the SS18-SSX-regulated intrinsic apoptotic pathway as a promising therapeutic strategy for SS. Full article
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14 pages, 3032 KiB  
Article
Beneficial Use of the Combination of Gemcitabine and Dacarbazine in Advanced Soft Tissue Sarcomas: Real-World Data
by Ibon Gurruchaga Sotés, M. Carmen Gómez-Mateo, María Eugenia Ortega Izquierdo and Javier Martínez-Trufero
Cancers 2024, 16(2), 267; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers16020267 - 8 Jan 2024
Viewed by 813
Abstract
Background: The combination of gemcitabine and dacarbazine has exhibited efficacy in terms of progression-free survival (PFS) and overall survival (OS) for aSTSs, albeit without robust confirmation from larger clinical trials. Methods: We conducted a retrospective study in a single institution involving aSTS patients [...] Read more.
Background: The combination of gemcitabine and dacarbazine has exhibited efficacy in terms of progression-free survival (PFS) and overall survival (OS) for aSTSs, albeit without robust confirmation from larger clinical trials. Methods: We conducted a retrospective study in a single institution involving aSTS patients treated with gemcitabine and dacarbazine. Results: 95 patients were assessed, pointing to a benefit in PFS of 3.5 months and an OS of 14.2 months. Patients with translocated histotypes had better PFS, while those with platelet–lymphocyte ratios (PLRs) surpassing a specific threshold or lower albumin levels had poorer overall survival. Conclusions: This study validates previous findings from three phase I–II trials, affirming the utility of this treatment approach in routine clinical practice. Full article
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19 pages, 5499 KiB  
Article
EWSR1::ATF1 Orchestrates the Clear Cell Sarcoma Transcriptome in Human Tumors and a Mouse Genetic Model
by Benjamin B. Ozenberger, Li Li, Emily R. Wilson, Alexander J. Lazar, Jared J. Barrott and Kevin B. Jones
Cancers 2023, 15(24), 5750; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15245750 - 8 Dec 2023
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Abstract
Clear cell sarcoma (CCS) is a rare, aggressive malignancy that most frequently arises in the soft tissues of the extremities. It is defined and driven by expression of one member of a family of related translocation-generated fusion oncogenes, the most common of which [...] Read more.
Clear cell sarcoma (CCS) is a rare, aggressive malignancy that most frequently arises in the soft tissues of the extremities. It is defined and driven by expression of one member of a family of related translocation-generated fusion oncogenes, the most common of which is EWSR1::ATF1. The EWSR1::ATF1 fusion oncoprotein reprograms transcription. However, the binding distribution of EWSR1::ATF1 across the genome and its target genes remain unclear. Here, we interrogated the genomic distribution of V5-tagged EWSR1::ATF1 in tumors it had induced upon expression in mice that also recapitulated the transcriptome of human CCS. ChIP-sequencing of V5-EWSR1::ATF1 identified previously unreported motifs including the AP1 motif and motif comprised of TGA repeats that resemble GGAA-repeating microsatellites bound by EWSR1::FLI1 in Ewing sarcoma. ChIP-sequencing of H3K27ac identified super enhancers in the mouse model and human contexts of CCS, which showed a shared super enhancer structure that associates with activated genes. Full article
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