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Molecular Biological Insights and Targeted Therapies for Sarcomas
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Molecular Biological Insights and Targeted Therapies for Sarcomas

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (20 June 2025) | Viewed by 2668

Special Issue Editor

Dr. Caterina Mancarella

E-Mail Website
Guest Editor
IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy
Interests: cancer biology; sarcoma; IGF system; RNA-binding proteins; drug resistance; cell cultures
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite the rarity and heterogeneity of sarcoma, current intensive chemotherapy and surgical procedures are able to significanly ameliorate the survival of patients with localized disease. On the contrary, metastatic disease remains a major challenge. Breakthroughs in genomic sequencing techniques, coupled with advances in experimental models, have improved our knowledge of the mechanisms of progression and metastasis of sarcomas. These approaches hold the promise to benefits the development of novel targeted therapies and personalized treatment for sarcoma patients.

This Special Issue aims to provide new impetus to molecular and personalized medicine development for sarcomas. We are eager to publish original research as well as reviews on molecular biology, mechanisms of metastases, microenvironment, and cutting-edge treatments for bone and soft-tissue sarcomas—including discussions of epigenetics, genetics, signaling pathways, and immunotherapies. Reports on new combination therapies and novel preclinical models are also welcome.

Dr. Caterina Mancarella
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

  • sarcoma
  • therapeutic target
  • preclinical models
  • molecular target

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Published Papers (2 papers)

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Research

17 pages, 2890 KiB  
Article
Potential Involvement of Myostatin in Smooth Muscle Differentiation in Pleomorphic Leiomyosarcoma
by Hiroko Onagi, Raku Son, Akiko Oguchi, Kei Sano, Keita Sasa, Nobuhiko Hasegawa, Keisuke Akaike, Daisuke Kubota, Tatsuya Takagi, Takuo Hayashi, Muneaki Ishijima, Takashi Yao, Yoshiyuki Suehara, Yasuhiro Murakawa and Tsuyoshi Saito
Int. J. Mol. Sci. 2025, 26(16), 7676; https://doi.org/10.3390/ijms26167676 - 8 Aug 2025
Viewed by 158
Abstract
High-grade sarcomas often lack typical morphological features and exhibit no clear differentiation, often leading to a diagnosis of undifferentiated sarcoma (US). Pleomorphic leiomyosarcoma (PLMS) is a high-grade sarcoma consisting of a typical leiomyosarcoma (LMS) component alongside dedifferentiated high-grade areas. A few decades ago, [...] Read more.
High-grade sarcomas often lack typical morphological features and exhibit no clear differentiation, often leading to a diagnosis of undifferentiated sarcoma (US). Pleomorphic leiomyosarcoma (PLMS) is a high-grade sarcoma consisting of a typical leiomyosarcoma (LMS) component alongside dedifferentiated high-grade areas. A few decades ago, PLMS was regarded as a subtype of high-grade sarcoma previously referred to as malignant fibrous histiocytoma; it is now classified as a variant of LMS. The mechanisms underlying myogenic differentiation and their relevance to the pathological diagnosis of high-grade sarcomas remain poorly understood. To investigate the gene expression networks associated with myogenic differentiation, we employed Cap Analysis of Gene Expression (CAGE) to distinguish PLMS from other high-grade sarcoma subtypes. We analyzed 27 frozen high-grade sarcoma samples, comprising 10 PLMSs, 11 high-grade myxofibrosarcomas, 3 dedifferentiated liposarcomas, 2 USs, and 1 high-grade sarcoma not otherwise specified, using CAGE profiling. Hierarchical clustering based on differentially expressed genes identified by CAGE separated 7 of the 10 PLMSs from other high-grade sarcomas, while the remaining 3 PLMSs clustered with a single US case. CAGE analysis also revealed that the myostatin (MSTN) promoter (false discovery rate [FDR] < 0.05) was more strongly activated in the high-grade sarcoma group lacking morphological and immunohistochemical smooth muscle differentiation than in the PLMS group, whereas the alpha smooth muscle actin (ACTA2) promoter (FDR < 0.05) was more prominently activated in the PLMS group. Immunohistochemical analysis showed reduced or absent myostatin expression in PLMSs, in contrast to diffuse myostatin expression in other high-grade sarcomas. Smooth muscle actin, encoded by ACTA2, was expressed in all 10 PLMS cases but only in 11 of 17 other high-grade sarcomas. Furthermore, both conventional immunohistochemistry and double immunostaining revealed that myostatin and myogenic markers exhibited largely mutually exclusive expression patterns within these tumors. A validation study was performed using 59 soft tissue sarcoma cases, including 27 PLMSs and 16 LMSs. Loss or reduction in myostatin expression was confirmed in both LMS and PLMS, and the ratio of myostatin loss was comparable (62.5% in LMS vs. 63% in PLMS). Collectively, these findings suggest that myostatin contributes to smooth muscle differentiation in high-grade sarcomas and has potential utility as a diagnostic marker. Full article
(This article belongs to the Special Issue Molecular Biological Insights and Targeted Therapies for Sarcomas)
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16 pages, 5230 KiB  
Article
Studies on Autophagy and Apoptosis of Fibrosarcoma HT-1080 Cells Mediated by Chalcone with Indole Moiety
by Ewelina Honkisz-Orzechowska, Olga Barczyk-Woźnicka, Maria Kaleta, Jadwiga Handzlik and Katarzyna Kieć-Kononowicz
Int. J. Mol. Sci. 2024, 25(11), 6100; https://doi.org/10.3390/ijms25116100 - 1 Jun 2024
Cited by 1 | Viewed by 1783
Abstract
This study demonstrated the anticancer efficacy of chalcones with indole moiety (MIPP, MOMIPP) in fibrosarcoma cells for the first time. The results showed that MIPP and MOMIPP reduced the viability of HT-1080 cells in a concentration-dependent manner. MOMIPP was more active than MIPP [...] Read more.
This study demonstrated the anticancer efficacy of chalcones with indole moiety (MIPP, MOMIPP) in fibrosarcoma cells for the first time. The results showed that MIPP and MOMIPP reduced the viability of HT-1080 cells in a concentration-dependent manner. MOMIPP was more active than MIPP in HT-1080 cells, showing lower IC50 values (3.67 vs. 29.90 μM). Both compounds at a concentration of 1 μM induced apoptosis in HT-1080 cells, causing death strictly related to caspase activation, as cell viability was restored when the caspase inhibitor Z-VAD was added. Reactive oxygen species production was approximately 3-fold higher than in control cells, and cotreatment with the inhibitor of mitochondrial ATPase oligomycin diminished this effect. Such effects were also reflected in mitochondrial dysfunction, including decreased membrane potential. Interestingly, the compounds that were studied caused massive vacuolization in HT-1080 cells. Immunocytochemical staining and TEM analysis showed that HT-1080 cells exhibited increased expression of the LC3-II protein and the presence of autophagosomes with a double membrane, respectively. Both compounds induced apoptosis, highlighting a promising link between autophagy and apoptosis. This connection could be a new target for therapeutic strategies to overcome chemoresistance, which is a significant cause of treatment failure and tumour recurrence in fibrosarcoma following traditional chemotherapy. Full article
(This article belongs to the Special Issue Molecular Biological Insights and Targeted Therapies for Sarcomas)
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