Epigenetic Abnormalities in Chondrosarcoma

Bereza, Michał; Dembiński, Mateusz; Zając, Agnieszka; Piątkowski, Jakub; Dudzisz-Śledź, Monika; Rutkowski, Piotr; Czarnecka, Anna M.

doi:10.3390/ijms24054539

Cited by 9 publications

(3 citation statements)

References 129 publications

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“…Venneker et al’s study highlights the crucial role of exploring epigenetic vulnerabilities in chondrosarcoma, going beyond the well-documented influence of IDH mutations [ 60 ]. Epigenetic dysregulation, a key aspect of cancer biology, contributes to the initiation and progression of various malignancies, making it paramount to understand these alterations in chondrosarcoma [ 61 ]. The study emphasizes the broader landscape of epigenetic vulnerabilities, detailing alterations in DNA methylation patterns, histone modifications, and chromatin remodeling processes impacting gene expression regulation [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies

Agosti,

Zeppieri,

Antonietti

et al. 2024

JPM

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Background: Chondrosarcomas rank as the second most common primary bone malignancy. Characterized by the production of a cartilaginous matrix, these tumors typically exhibit resistance to both radiotherapy (RT) and chemotherapy (CT), resulting in overall poor outcomes: a high rate of mortality, especially among children and adolescents. Due to the considerable resistance to current conventional therapies such as surgery, CT, and RT, there is an urgent need to identify factors contributing to resistance and discover new strategies for optimal treatment. Over the past decade, researchers have delved into the dysregulation of genes associated with tumor development and therapy resistance to identify potential therapeutic targets for overcoming resistance. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including isocitrate dehydrogenase (IDH1/2) and COL2A1. Molecule-targeting agents and immunotherapies have demonstrated favorable antitumor activity in clinical studies involving patients with advanced chondrosarcomas. In this systematic review, we delineate the clinical features of chondrosarcoma and provide a summary of gene dysregulation and mutation associated with tumor development, as well as targeted therapies as a promising molecular approach. Finally, we analyze the probable role of the tumor microenvironment in chondrosarcoma drug resistance. Methods: A systematic search was conducted across major medical databases (PubMed, Embase, and Cochrane Library) up to 10 November 2023. The search strategy utilized relevant Medical Subject Heading (MeSH) terms and keywords related to “chondrosarcomas”, “target therapies”, “immunotherapies”, and “outcomes”. The studies included in this review consist of randomized controlled trials, non-randomized controlled trials, and cohort studies reporting on the use of target therapies for the treatment of chondrosarcoma in human subjects. Results: Of the initial 279 articles identified, 40 articles were included in the article. The exclusion of 140 articles was due to reasons such as irrelevance, non-reporting of selected results, systematic literature review or meta-analysis, and lack of details on the method/results. Three tables highlighted clinical studies, preclinical studies, and ongoing clinical trials, encompassing 13, 7, and 20 studies, respectively. For the clinical study, a range of molecular targets, such as death receptors 4/5 (DR4 and DR5) (15%), platelet-derived growth factor receptor-alpha or -beta (PDGFR-α, PDGFR-β) (31%), were investigated. Adverse events were mainly constitutional symptoms emphasizing that to improve therapy tolerance, careful observation and tailored management are essential. Preclinical studies analyzed various molecular targets such as DR4/5 (28.6%) and COX-2 (28.6%). The prevalent indicator of antitumoral activity was the apoptotic rate of both a single agent (tumor necrosis factor-related apoptosis-inducing ligand: TRAIL) and double agents (TRAIL-DOX, TRAIL-MG132). Ongoing clinical trials, the majority in Phase II (53.9%), highlighted possible therapeutic strategies such as IDH1 inhibitors and PD-1/PD-L1 inhibitors (30.8%). Conclusions: The present review offers a comprehensive analysis of targeted therapeutics for skull base chondrosarcomas, highlighting a complex landscape characterized by a range of treatment approaches and new opportunities for tailored interventions. The combination of results from molecular research and clinical trials emphasizes the necessity for specialized treatment strategies and the complexity of chondrosarcoma biology.

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Section: Discussionmentioning

confidence: 99%

Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies

Agosti,

Zeppieri,

Antonietti

et al. 2024

JPM

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“…Outcomes of chondrosarcoma patients depend on grade, stage, and surgical margins because higher grade shows (10,19,20) decreased patient survival. Based on a recent meta-analysis, survival with different histologic grades was as follows: 5-year survival for chondrosarcomas grade 1 was 82% to 99%, 2-63% to 92%, and 3-0% to 77% (6).…”

Section: Discussionmentioning

confidence: 99%

Chondrosarcoma: an analysis of clinical characteristics, treatment outcomes, and prognostic factors in a decade-long single center experience

Depboylu,

Tasan,

Tataroglu

2023

ATJMED

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Aim: Management of chondrosarcoma patients is associated with histologic subtypes and clinical behaviors. This study describes our institution's management and outcome experience for 12 chondrosarcoma patients with higher grades in rarer locations. Materials and Methods: Pathologically diagnosed chondrosarcoma patients between January 2013 and January 2023 were retrospectively scanned. Patients under 18 years, duplicate records, second primary malignancy, index surgery at another hospital were excluded, and data of remaining 12 patients were statistically analyzed. Results: Twelve patients (6 female, 6 male) had median age of 62 (21-94) years. Locations of primary tumors were femur (n=4), larynx (n=1), left gluteus (n=1), lung (n=1), periscapular soft tissue (n=1), tarsal bone (n=1), distal metacarps (n=1), scapula (n=1), and sternum (n=1). There were local relapses in three cases (chest wall, ipsilateral femur, acetabulum, and ipsilateral gluteal region) and distant metastasis in three cases (contralateral lung, lung, bilateral lung, and pleura) during the follow-up. The median tumor size was 5.65cm (1.5-21.5cm). Histologic subtypes were Chondrosarcoma (Grade I) (n=4), Chondrosarcoma (Grade II) (n=1), Chondrosarcoma (Grade III) (n=2), Dedifferentiated Chondrosarcoma (Grade III) (n=2), Extraskeletal Mesenchymal Chondrosarcoma (n=3). Surgical treatment was eight wide resections, one lobectomy, one laryngectomy, one amputation, and one curettage. Five patients received chemotherapy (2 neoadjuvant chemotherapy, 3 adjuvant chemotherapy), two patients received low dose (50.4Gy) (3DCRT; IMRT), and two patients received high dose (>60Gy) (IMRT) adjuvant radiation therapy. The median follow-up was 26.5 months (2-121 months). The median survival was 26.5 months (2-121 months). Median relapse-free survival was three months (0-96 months). The overall and relapse-free survivals at two years were 81.5% and 50%; at five years, 71.3% and 25%. Conclusion: Our results demonstrate that surgery is the gold standard treatment, but well-managed adjuvant oncologic treatment provides undeniable advantage for overall survival in selected cases.

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“…Nowadays, in addition to stem-like characteristics, it has been ascertained that genomic heterogeneity and epigenetic modifications in ChS cells, as well as deregulation of pivotal signal transduction pathways, are implicated in the drug- and radio-resistance of ChS cells [ 8 , 30 , 36 ]. This provided the rationale for developing new drugs, such as inhibitors of tyrosine kinase, activating mutated genes, mammalian target of rapamycin (mTOR), or histone deacetylase (HDAC) [ 37 ] ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Emerging Treatments Targeting the Tumor Microenvironment for Advanced Chondrosarcoma

Ingangi,

De Chiara,

Ferrara

et al. 2024

Cells

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Chondrosarcoma (ChS), a malignant cartilage-producing tumor, is the second most frequently diagnosed osseous sarcoma after osteosarcoma. It represents a very heterogeneous group of malignant chemo- and radiation-resistant neoplasms, accounting for approximately 20% of all bone sarcomas. The majority of ChS patients have a good prognosis after a complete surgical resection, as these tumors grow slowly and rarely metastasize. Conversely, patients with inoperable disease, due to the tumor location, size, or metastases, represent a great clinical challenge. Despite several genetic and epigenetic alterations that have been described in distinct ChS subtypes, very few therapeutic options are currently available for ChS patients. Therefore, new prognostic factors for tumor progression as well as new treatment options have to be explored, especially for patients with unresectable or metastatic disease. Recent studies have shown that a correlation between immune infiltrate composition, tumor aggressiveness, and survival does exist in ChS patients. In addition, the intra-tumor microvessel density has been proven to be associated with aggressive clinical behavior and a high metastatic potential in ChS. This review will provide an insight into the ChS microenvironment, since immunotherapy and antiangiogenic agents are emerging as interesting therapeutic options for ChS patients.

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Epigenetic Abnormalities in Chondrosarcoma

Cited by 9 publications

References 129 publications

Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies

Advancing the Management of Skull Base Chondrosarcomas: A Systematic Review of Targeted Therapies

Chondrosarcoma: an analysis of clinical characteristics, treatment outcomes, and prognostic factors in a decade-long single center experience

Emerging Treatments Targeting the Tumor Microenvironment for Advanced Chondrosarcoma

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