Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
New Strategies in Therapeutic Targets of Sarcoma: Translational Implications 2.0
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

New Strategies in Therapeutic Targets of Sarcoma: Translational Implications 2.0

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 (28 February 2023) | Viewed by 12126

Special Issue Editor

Dr. Cecilia Garofalo

E-Mail Website
Guest Editor
Advanced Translational Research Laboratory, Veneto Institute of Oncology IOV—IRCCS, 35127 Padua, Italy
Interests: sarcoma; prognostic and predictive cancer biomarkers; pharmacogenomics; chemoresistance; targeted therapy; anticancer drugs; signal transduction; IGF system in cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sarcomas are an uncommon and heterogeneous group of mesenchymal malignant tumors originating from bone, cartilage and other mesenchymal tissues, such as muscle, fat, peripheral nerves, and fibrous or related tissues. The two main types of sarcomas are soft tissue and bone sarcomas, but there are more than 70 different entities within these two categories. Even if the incidence is low, sarcoma presents a high mortality rate due to high metastatic potential, late diagnosis, and relapse. Survival for treated patients with metastatic disease is only 14–17 months, and the 2-year survival rate is about 30%.

Over the last two decades, the increased knowledge of the new primary molecular and genomic mechanisms of different sarcoma histotypes has resulted in the reclassification of these tumors and, consequently, the discovery of innovative chemotherapeutic agents. However, despite the continued progress in discovering genetic aberrations and their functions in these tumors, the primary therapeutic option for the majority of local recurrence and metastatic sarcomas remains cytotoxic chemotherapy. Moreover, the response rates to novel molecular-targeting drugs are not very extraordinary, and new treatment strategies are required. Thus, there is an urgent need to develop novel treatments and find biomarkers to help physicians identify patients who are possible good responders or resistant to specific therapies and predict individual predisposition to toxicity reactions associated with therapies.

This Special Issue aims to summarize the recent advancements in new therapeutic options and biomarkers in Bone and Soft Tissue Sarcoma (STS). We welcome original research articles and reviews covering clinical, translational, and basic studies, focusing on, but not limited to:

  1. In vitro-, in vivo-, or ex vivo-validated studies on emerging therapeutic targets for Bone and Soft Tissue Sarcoma, including immune checkpoints, oncogenes, tumor suppressor genes, non-coding RNAs (miRNA, lncRNA, circRNA), and exosomes;
  2. Innovative therapeutics include small molecules, antibodies (such as PD-1/PD-L1 antibodies), as well as cell therapy (CAR-T and other gene-engineered cells);
  3. Prognostic and predictive biomarkers;
  4. Clinical evaluation of novel treatments efficacy with biomolecular experiments;
  5. New drug delivery systems to achieve precise control of drug release at specific tissue sites and time points, including nanoparticles, micelles, and other natural or artificial materials.

Dr. Cecilia Garofalo
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

  • soft tissue sarcoma
  • GIST
  • prognostic and predictive cancer biomarkers
  • resistance to chemotherapy
  • precision medicine
  • targeted therapy
  • pharmacogenomics

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 4263 KiB  
Article
Unveiling the Genomic Basis of Chemosensitivity in Sarcomas of the Extremities: An Integrated Approach for an Unmet Clinical Need
by Silvia Vanni, Valentina Fausti, Eugenio Fonzi, Chiara Liverani, Giacomo Miserocchi, Chiara Spadazzi, Claudia Cocchi, Chiara Calabrese, Lorena Gurrieri, Nada Riva, Federica Recine, Roberto Casadei, Federica Pieri, Ania Naila Guerrieri, Massimo Serra, Toni Ibrahim, Laura Mercatali and Alessandro De Vita
Int. J. Mol. Sci. 2023, 24(8), 6926; https://doi.org/10.3390/ijms24086926 - 8 Apr 2023
Cited by 11 | Viewed by 2120
Abstract
Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) can be considered as a spectrum of the same disease entity, representing one of the most common adult soft tissue sarcoma (STS) of the extremities. While MFS is rarely metastasizing, it shows an extremely high rate [...] Read more.
Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) can be considered as a spectrum of the same disease entity, representing one of the most common adult soft tissue sarcoma (STS) of the extremities. While MFS is rarely metastasizing, it shows an extremely high rate of multiple frequent local recurrences (50–60% of cases). On the other hand, UPS is an aggressive sarcoma prone to distant recurrence, which is correlated to a poor prognosis. Differential diagnosis is challenging due to their heterogeneous morphology, with UPS remaining a diagnosis of exclusion for sarcomas with unknown differentiation lineage. Moreover, both lesions suffer from the unavailability of diagnostic and prognostic biomarkers. In this context, a genomic approach combined with pharmacological profiling could allow the identification of new predictive biomarkers that may be exploited for differential diagnosis, prognosis and targeted therapy, with the aim to improve the management of STS patients. RNA-Seq analysis identified the up-regulation of MMP13 and WNT7B in UPS and the up-regulation of AKR1C2, AKR1C3, BMP7, and SGCG in MFS, which were confirmed by in silico analyses. Moreover, we identified the down-regulation of immunoglobulin genes in patient-derived primary cultures that responded to anthracycline treatment compared to non-responder cultures. Globally, the obtained data corroborated the clinical observation of UPS as an histotype refractory to chemotherapy and the key role of the immune system in determining chemosensitivity of these lesions. Moreover, our results confirmed the validity of genomic approaches for the identification of predictive biomarkers in poorly characterized neoplasms as well as the robustness of our patient-derived primary culture models in recapitulating the chemosensitivity features of STS. Taken as a whole, this body of evidence may pave the way toward an improvement of the prognosis of these rare diseases through a treatment modulation driven by a biomarker-based patient stratification. Full article
(This article belongs to the Special Issue New Strategies in Therapeutic Targets of Sarcoma: Translational Implications 2.0)
►▼ Show Figures

Figure 1

28 pages, 4737 KiB  
Article
Surfaceome Profiling of Cell Lines and Patient-Derived Xenografts Confirm FGFR4, NCAM1, CD276, and Highlight AGRL2, JAM3, and L1CAM as Surface Targets for Rhabdomyosarcoma
by Andrea Timpanaro, Caroline Piccand, Anne-Christine Uldry, Peter Karl Bode, Dzhangar Dzhumashev, Rita Sala, Manfred Heller, Jochen Rössler and Michele Bernasconi
Int. J. Mol. Sci. 2023, 24(3), 2601; https://doi.org/10.3390/ijms24032601 - 30 Jan 2023
Cited by 8 | Viewed by 3740
Abstract
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The prognosis for patients with high-grade and metastatic disease is still very poor, and survivors are burdened with long-lasting side effects. Therefore, more effective and less toxic therapies are needed. Surface proteins [...] Read more.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The prognosis for patients with high-grade and metastatic disease is still very poor, and survivors are burdened with long-lasting side effects. Therefore, more effective and less toxic therapies are needed. Surface proteins are ideal targets for antibody-based therapies, like bispecific antibodies, antibody-drug conjugates, or chimeric antigen receptor (CAR) T-cells. Specific surface targets for RMS are scarce. Here, we performed a surfaceome profiling based on differential centrifugation enrichment of surface/membrane proteins and detection by LC-MS on six fusion-positive (FP) RMS cell lines, five fusion-negative (FN) RMS cell lines, and three RMS patient-derived xenografts (PDXs). A total of 699 proteins were detected in the three RMS groups. Ranking based on expression levels and comparison to expression in normal MRC-5 fibroblasts and myoblasts, followed by statistical analysis, highlighted known RMS targets such as FGFR4, NCAM1, and CD276/B7-H3, and revealed AGRL2, JAM3, MEGF10, GPC4, CADM2, as potential targets for immunotherapies of RMS. L1CAM expression was investigated in RMS tissues, and strong L1CAM expression was observed in more than 80% of alveolar RMS tumors, making it a practicable target for antibody-based therapies of alveolar RMS. Full article
(This article belongs to the Special Issue New Strategies in Therapeutic Targets of Sarcoma: Translational Implications 2.0)
►▼ Show Figures

Figure 1

Review

Jump to: Research

26 pages, 762 KiB  
Review
Emerging Targeted Therapeutic Strategies to Overcome Imatinib Resistance of Gastrointestinal Stromal Tumors
by Maria Teresa Masucci, Maria Letizia Motti, Michele Minopoli, Gioconda Di Carluccio and Maria Vincenza Carriero
Int. J. Mol. Sci. 2023, 24(7), 6026; https://doi.org/10.3390/ijms24076026 - 23 Mar 2023
Cited by 4 | Viewed by 3209
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal neoplasms of the gastrointestinal tract. The gold standard for the diagnosis of GISTs is morphologic analysis with an immunohistochemical evaluation plus genomic profiling to assess the mutational status of lesions. The majority of [...] Read more.
Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal neoplasms of the gastrointestinal tract. The gold standard for the diagnosis of GISTs is morphologic analysis with an immunohistochemical evaluation plus genomic profiling to assess the mutational status of lesions. The majority of GISTs are driven by gain-of-function mutations in the proto-oncogene c-KIT encoding the tyrosine kinase receptor (TKR) known as KIT and in the platelet-derived growth factor-alpha receptor (PDGFRA) genes. Approved therapeutics are orally available as tyrosine kinase inhibitors (TKIs) targeting KIT and/or PDGFRA oncogenic activation. Among these, imatinib has changed the management of patients with unresectable or metastatic GISTs, improving their survival time and delaying disease progression. Nevertheless, the majority of patients with GISTs experience disease progression after 2–3 years of imatinib therapy due to the development of secondary KIT mutations. Today, based on the identification of new driving oncogenic mutations, targeted therapy and precision medicine are regarded as the new frontiers for GISTs. This article reviews the most important mutations in GISTs and highlights their importance in the current understanding and treatment options of GISTs, with an emphasis on the most recent clinical trials. Full article
(This article belongs to the Special Issue New Strategies in Therapeutic Targets of Sarcoma: Translational Implications 2.0)
►▼ Show Figures

Figure 1

21 pages, 768 KiB  
Review
Exosome-Based Liquid Biopsy Approaches in Bone and Soft Tissue Sarcomas: Review of the Literature, Prospectives, and Hopes for Clinical Application
by Chiara Agnoletto, Ymera Pignochino, Chiara Caruso and Cecilia Garofalo
Int. J. Mol. Sci. 2023, 24(6), 5159; https://doi.org/10.3390/ijms24065159 - 8 Mar 2023
Cited by 4 | Viewed by 2356
Abstract
The knowledge of exosome impact on sarcoma development and progression has been implemented in preclinical studies thanks to technological advances in exosome isolation. Moreover, the clinical relevance of liquid biopsy is well established in early diagnosis, prognosis prediction, tumor burden assessment, therapeutic responsiveness, [...] Read more.
The knowledge of exosome impact on sarcoma development and progression has been implemented in preclinical studies thanks to technological advances in exosome isolation. Moreover, the clinical relevance of liquid biopsy is well established in early diagnosis, prognosis prediction, tumor burden assessment, therapeutic responsiveness, and recurrence monitoring of tumors. In this review, we aimed to comprehensively summarize the existing literature pointing out the clinical relevance of detecting exosomes in liquid biopsy from sarcoma patients. Presently, the clinical utility of liquid biopsy based on exosomes in patients affected by sarcoma is under debate. The present manuscript collects evidence on the clinical impact of exosome detection in circulation of sarcoma patients. The majority of these data are not conclusive and the relevance of liquid biopsy-based approaches in some types of sarcoma is still insufficient. Nevertheless, the utility of circulating exosomes in precision medicine clearly emerged and further validation in larger and homogeneous cohorts of sarcoma patients is clearly needed, requiring collaborative projects between clinicians and translational researchers for these rare cancers. Full article
(This article belongs to the Special Issue New Strategies in Therapeutic Targets of Sarcoma: Translational Implications 2.0)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop