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Cancers
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Osteosarcoma: Individualized Precision Treatment and Effective Drug Discovery
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Osteosarcoma: Individualized Precision Treatment and Effective Drug Discovery

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

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1690

Special Issue Editor

Dr. Margherita Cortini

E-Mail Website
Guest Editor
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
Interests: osteosarcoma; bone cancer; tumor microenvironment; tumor acidosis; lipid metabolism; targeted therapies; precision medicine; microfluidics; 3D tumor models

Special Issue Information

Dear Colleagues,

Osteosarcoma is a highly aggressive cancer of mesenchymal origin that develops in bone. Despite decades of research, the survival rates for patients with osteosarcoma have remained largely unchanged. While surgery and conventional therapies remain the cornerstone of treatment, they offer limited benefits for patients with metastatic disease. This underscores the urgent need for innovative therapies to improve survival rates and reduce metastatic spread.

This Special Issue seeks to explore the latest advancements and future directions in understanding the molecular mechanisms underlying bone and soft tissue sarcomas. By delving into the molecular landscape of these tumors, we aim to highlight novel therapeutic strategies and their potential to transform the treatment of these challenging diseases.

Recent years have witnessed remarkable progress in targeted therapies and drug discovery for osteosarcoma. Advances in the molecular characterization of the disease have unveiled promising new targets and treatment avenues.

In this Special Issue, we bring together cutting-edge research and insights to summarize recent breakthroughs in precision medicine and innovative drug discovery for osteosarcoma, offering hope for improved patient outcomes and a brighter future in the fight against this formidable malignancy.

Dr. Margherita Cortini
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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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

  • osteosarcoma
  • bone cancer
  • tumor microenvironment
  • targeted therapies
  • precision medicine
  • 3D tumor models
  • drug screening

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Published Papers (2 papers)

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Review

31 pages, 1304 KB  
Review
Exploring Emerging Therapeutic Targets in Osteosarcoma by Revisiting the Immune and Cancer-Intrinsic Hallmarks of Cancer
by Lidia Tarone, Antonella Iacoviello, Antonino Di Lorenzo, Roberta Verta, Chiara Cossu, Laura Conti, Federica Cavallo and Federica Riccardo
Cancers 2025, 17(23), 3846; https://doi.org/10.3390/cancers17233846 - 30 Nov 2025
Viewed by 455
Abstract
Osteosarcoma (OSA) is an aggressive primary bone cancer mainly affecting the pediatric population. Despite intensive multimodal treatments, therapeutic progress has remained limited for decades, resulting in high recurrence rates, poor prognosis driven by metastatic progression, and severe chemotherapy-associated toxicities. To advance the development [...] Read more.
Osteosarcoma (OSA) is an aggressive primary bone cancer mainly affecting the pediatric population. Despite intensive multimodal treatments, therapeutic progress has remained limited for decades, resulting in high recurrence rates, poor prognosis driven by metastatic progression, and severe chemotherapy-associated toxicities. To advance the development of more effective and safer therapeutic strategies, our recent studies identified Chondroitin Sulfate Proteoglycan (CSPG)4 as a relevant mediator of the malignant behavior of OSA cells. Targeting CSPG4 DNA-based vaccine demonstrated encouraging antitumor activity against OSA. Nevertheless, since single-agent immunotherapies are often constrained by tumor immune escape, the need for rational combinatorial strategies is of utmost importance. In this perspective, we broaden our analysis to include other potentially complementary targets beyond CSPG4, which may contribute to OSA pathogenesis. Among these, the cystine/glutamate antiporter xCT and Toll-like Receptor 2 (TLR2) emerge as particularly promising due to their established role in tumor progression, therapy resistance, and immune modulation. We discuss the contribution of all these molecules in major hallmarks of OSA—(1) proliferative and survival advantages, (2) metastasis and angiogenesis, and (3) immune evasion—and examine potential strategies for their combined targeting. By leveraging knowledge gained from other cancer models and integrating it with the distinct biological and clinical features of OSA, this perspective seeks to outline rational and innovative combinatorial strategies that may overcome current therapeutic limitations and ultimately improve patient outcomes. Full article
(This article belongs to the Special Issue Osteosarcoma: Individualized Precision Treatment and Effective Drug Discovery)
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24 pages, 3626 KB  
Review
The Unfolded Protein Response in Sarcomas: From Proteostasis to Therapy Resistance
by Elizabeta Ilieva, Sofia Avnet, Nicola Baldini and Margherita Cortini
Cancers 2025, 17(21), 3489; https://doi.org/10.3390/cancers17213489 - 30 Oct 2025
Viewed by 921
Abstract
Sarcomas are a rare and heterogeneous group of malignant tumors that pose significant clinical challenges, including delayed diagnosis, therapeutic resistance, and lack of reliable biomarkers. Despite advances in surgery and chemotherapy, effective treatment options for advanced disease remain limited, underscoring the urgent need [...] Read more.
Sarcomas are a rare and heterogeneous group of malignant tumors that pose significant clinical challenges, including delayed diagnosis, therapeutic resistance, and lack of reliable biomarkers. Despite advances in surgery and chemotherapy, effective treatment options for advanced disease remain limited, underscoring the urgent need to identify novel therapeutic vulnerabilities. The unfolded protein response (UPR), a conserved cellular stress pathway that maintains proteostasis under conditions of endoplasmic reticulum stress, has emerged as a critical modulator of cancer cell fate. By regulating protein folding, redox balance, and survival pathways, the UPR exerts a dual role in tumor biology, supporting tumor growth under stress while triggering apoptosis when stress becomes sustained or severe. In sarcomas, accumulating evidence indicates that UPR activation contributes to metabolic adaptation, angiogenesis, immune evasion, and chemoresistance. Drawing on the current literature encompassing preclinical models, recent translational research (PubMed from 2000 to 2025), and registered clinical trials, this narrative review synthesizes current knowledge on the multifaceted role of the UPR in sarcoma pathogenesis, with a particular focus on osteosarcoma. Furthermore, it explores the feasibility of UPR-targeted strategies as adjuvant or combinatorial approaches. In conclusion, this review provides an integrated and in-depth analysis of UPR-mediated mechanisms in sarcomas, offering perspectives on how targeting this pathway could accelerate the development of more effective and personalized treatments. Full article
(This article belongs to the Special Issue Osteosarcoma: Individualized Precision Treatment and Effective Drug Discovery)
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