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Abstract：
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.
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.
摘要：
背景：软骨肉瘤是第二常见的原发性骨恶性肿瘤。以软骨基质的产生为特征，这些肿瘤通常表现出对放疗（RT）和化疗（CT）的抵抗力，导致总体不良结果：高死亡率，尤其是儿童和青少年。由于对目前的传统疗法如手术有相当大的抵抗力，CT,RT,迫切需要确定导致耐药性的因素，并发现最佳治疗的新策略。在过去的十年里，研究人员深入研究了与肿瘤发展和治疗抵抗相关的基因失调，以确定克服抵抗的潜在治疗靶点。最近的研究提出了几种有希望的生物标志物和治疗目标的软骨肉瘤。包括异柠檬酸脱氢酶(IDH1/2)和COL2A1。在涉及晚期软骨肉瘤患者的临床研究中，分子靶向剂和免疫疗法已显示出良好的抗肿瘤活性。在这次系统审查中，我们描述了软骨肉瘤的临床特征，并提供了与肿瘤发展相关的基因失调和突变的总结。以及靶向治疗作为一种有前途的分子方法。最后,我们分析了肿瘤微环境在软骨肉瘤耐药中的可能作用。
方法：在主要医学数据库中进行了系统搜索(PubMed，Embase,和Cochrane图书馆）至2023年11月10日。搜索策略利用了与“软骨肉瘤”相关的相关医学主题标题(MeSH)术语和关键词，“目标疗法”，“免疫疗法”，和“结果”。纳入本综述的研究包括随机对照试验，非随机对照试验，和队列研究报告使用靶向疗法治疗人类受试者的软骨肉瘤。
结果：在确定的最初279篇文章中，该文章包括40篇文章。排除140篇文章是由于不相关等原因，未报告选定的结果，系统文献综述或荟萃分析，缺乏方法/结果的细节。三张表突出显示了临床研究，临床前研究,和正在进行的临床试验，包括13、7和20项研究，分别。对于临床研究，一系列分子靶标，如死亡受体4/5（DR4和DR5）（15％），血小板衍生生长因子受体α或β(PDGFR-α，PDGFR-β）（31%），被调查了。不良事件主要是体质症状，强调提高治疗耐受性，仔细观察和量身定制的管理至关重要。临床前研究分析了各种分子靶标，例如DR4/5（28.6％）和COX-2（28.6％）。抗肿瘤活性的普遍指标是单剂（肿瘤坏死因子相关的凋亡诱导配体：TRAIL）和双剂（TRAIL-DOX，TRAIL-MG132）。正在进行的临床试验，第二阶段大部分(53.9%)，强调了可能的治疗策略，如IDH1抑制剂和PD-1/PD-L1抑制剂（30.8%）。
结论：本综述对颅底软骨肉瘤的靶向治疗进行了全面分析，突出了一个复杂的景观，其特点是一系列的治疗方法和定制干预措施的新机会。分子研究和临床试验结果的结合强调了专门治疗策略的必要性和软骨肉瘤生物学的复杂性。
方法：在主要医学数据库中进行了系统搜索(PubMed，Embase,和Cochrane图书馆）至2023年11月10日。搜索策略利用了与“软骨肉瘤”相关的相关医学主题标题(MeSH)术语和关键词，“目标疗法”，“免疫疗法”，和“结果”。纳入本综述的研究包括随机对照试验，非随机对照试验，和队列研究报告使用靶向疗法治疗人类受试者的软骨肉瘤。
结果：在确定的最初279篇文章中，该文章包括40篇文章。排除140篇文章是由于不相关等原因，未报告选定的结果，系统文献综述或荟萃分析，缺乏方法/结果的细节。三张表突出显示了临床研究，临床前研究,和正在进行的临床试验，包括13、7和20项研究，分别。对于临床研究，一系列分子靶标，如死亡受体4/5（DR4和DR5）（15％），血小板衍生生长因子受体α或β(PDGFR-α，PDGFR-β）（31%），被调查了。不良事件主要是体质症状，强调提高治疗耐受性，仔细观察和量身定制的管理至关重要。临床前研究分析了各种分子靶标，例如DR4/5（28.6％）和COX-2（28.6％）。抗肿瘤活性的普遍指标是单剂（肿瘤坏死因子相关的凋亡诱导配体：TRAIL）和双剂（TRAIL-DOX，TRAIL-MG132）。正在进行的临床试验，第二阶段大部分(53.9%)，强调了可能的治疗策略，如IDH1抑制剂和PD-1/PD-L1抑制剂（30.8%）。
结论：本综述对颅底软骨肉瘤的靶向治疗进行了全面分析，突出了一个复杂的景观，其特点是一系列的治疗方法和定制干预措施的新机会。分子研究和临床试验结果的结合强调了专门治疗策略的必要性和软骨肉瘤生物学的复杂性。
