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Cancers
Special Issues
Molecular Mechanisms in Bone and Soft Tissue Sarcomas
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Molecular Mechanisms in Bone and Soft Tissue Sarcomas

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

Deadline for manuscript submissions: 30 June 2025 | Viewed by 3360

Special Issue Editors

Dr. Alexander L. Lazarides

E-Mail Website
Guest Editor
Sarcoma Department, Moffitt Cancer Center, Tampa, FL, USA
Interests: soft tissue sarcomas; bone sarcomas; surgical outcomes
Special Issues, Collections and Topics in MDPI journals
Dr. Zachary D.C. Burke

E-Mail Website
Guest Editor
Department of Orthopedic Surgery, Cleveland Clinic, Cleveland, OH, USA
Interests: orthopaedic surgery; antibiotics; antimicrobial

Special Issue Information

Dear Colleagues,

Bone and soft tissue sarcomas are rare, but disproportionately lethal cancers. Despite having a common cell of origin, there are a multitude of subtypes characterized by a significant genetic heterogeneity. This tumor heterogeneity has limited treatment progress, as a “one size fits all” approach has demonstrated limited efficacy. While surgery and adjuvant therapies are typically considered the mainstay of treatment, evolving understanding of the molecular underpinnings of these tumors, is revolutionizing the care of these tumors.

This Special Issue aims to update the current knowledge and future implications of the molecular underpinnings of bone and soft tissue sarcomas in order to highlight the current understanding of these tumors on a molecular level and the promising therapeutic approaches in the treatment of these challenging disease entities. Continued research is needed to identify the current obstacles and explore novel solutions to help optimize patient care, with a focus on how improved understanding of the molecular basis for these tumors translates to the clinical realm.

Dr. Alexander L. Lazarides
Dr. Zachary D.C. Burke
Guest Editors

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 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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • sarcoma
  • bone sarcoma
  • soft tissue sarcoma
  • osteosarcoma
  • molecular level
  • translation

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Published Papers (2 papers)

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Research

11 pages, 27353 KiB  
Article
Immunological Tumor Microenvironment of Solitary Fibrous Tumors—Associating Immune Infiltrate with Variables of Prognostic Significance
by Emilio Medina-Ceballos, Isidro Machado, Francisco Giner, Álvaro Blázquez-Bujeda, Mónica Espino, Samuel Navarro and Antonio Llombart-Bosch
Cancers 2024, 16(18), 3222; https://doi.org/10.3390/cancers16183222 - 21 Sep 2024
Cited by 1 | Viewed by 1347
Abstract
Background and objectives: Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting [...] Read more.
Background and objectives: Solitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs). Methods: A retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10–49, 2 = 50–99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round–oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS. Results: Only one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round–oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1. Conclusions: SFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Bone and Soft Tissue Sarcomas)
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21 pages, 6263 KiB  
Article
Targeting Asparagine Metabolism in Well-Differentiated/Dedifferentiated Liposarcoma
by Kyle D. Klingbeil, Blake R. Wilde, Danielle S. Graham, Serena Lofftus, Tyler McCaw, Nedas Matulionis, Sarah M. Dry, Joseph G. Crompton, Fritz C. Eilber, Thomas G. Graeber, David B. Shackelford, Heather R. Christofk and Brian E. Kadera
Cancers 2024, 16(17), 3031; https://doi.org/10.3390/cancers16173031 - 30 Aug 2024
Cited by 1 | Viewed by 1428
Abstract
Background: mTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS). Methods: Human [...] Read more.
Background: mTORC1 activity is dependent on the presence of micronutrients, including Asparagine (Asn), to promote anabolic cell signaling in many cancers. We hypothesized that targeting Asn metabolism would inhibit tumor growth by reducing mTORC1 activity in well-differentiated (WD)/dedifferentiated (DD) liposarcoma (LPS). Methods: Human tumor metabolomic analysis was utilized to compare abundance of Asn in WD vs. DD LPS. Gene set enrichment analysis (GSEA) compared relative expression among metabolic pathways upregulated in DD vs. WD LPS. Proliferation assays were performed for LPS cell lines and organoid models by using the combination treatment of electron transport chain (ETC) inhibitors with Asn-free media. 13C-Glucose-labeling metabolomics evaluated the effects of combination treatment on nucleotide synthesis. Murine xenograft models were used to assess the effects of ETC inhibition combined with PEGylated L-Asparaginase (PEG-Asnase) on tumor growth and mTORC1 signaling. Results: Asn was enriched in DD LPS compared to WD LPS. GSEA indicated that mTORC1 signaling was upregulated in DD LPS. Within available LPS cell lines and organoid models, the combination of ETC inhibition with Asn-free media resulted in reduced cell proliferation. Combination treatment inhibited nucleotide synthesis and promoted cell cycle arrest. In vivo, the combination of ETC inhibition with PEG-Asnase restricted tumor growth. Conclusions: Asn enrichment and mTORC1 upregulation are important factors contributing to WD/DD LPS tumor progression. Effective targeting strategies require limiting access to extracellular Asn and inhibition of de novo synthesis mechanisms. The combination of PEG-Asnase with ETC inhibition is an effective therapy to restrict tumor growth in WD/DD LPS. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Bone and Soft Tissue Sarcomas)
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