■横纹肌肉瘤(RMS)是最常见的小儿软组织恶性肿瘤,具有高度的临床病理学和分子异质性。临床前体内模型对于提高我们对RMS肿瘤生物学的理解和开发新的治疗策略至关重要。然而,关于临床前RMS研究的学术数据的多样性可能会对科学家和临床医生提出挑战.因此,我们对当代RMS小鼠模型进行了系统的文献调查,以表征其表型并评估其翻译相关性.
■我们通过搜索PubMed和WebofScience数据库,确定了在2018年1月7日至2023年1月7日之间发表的论文。
■在筛选的713条记录中,118项研究(26.9%)被纳入定性综合。细胞系来源的异种移植物(CDX)是最常用的(n=75,63.6%),其次是患者来源的异种移植物(PDX)和同基因模型,各占11.9%(n=14),和基因工程小鼠模型(GEMM)(n=7,5.9%)。在5.9%(n=7)的研究中报告了不同模型类别的组合。一项研究采用了病毒诱导的RMS模型。总的来说,40.0%(n=30)的研究利用CDX模型建立肺泡RMS(aRMS),而38.7%(n=29)为胚胎表型(eRMS)。有20.0%(n=15)的研究涉及aRMS和eRMS亚型的组合。在一项研究中(1.3%),RMS表型为梭形细胞/硬化。皮下异种移植物(n=66,55.9%)的使用频率高于原位模型(n=29,24.6%)。值得注意的是,所使用的细胞系均不来源于未经治疗的原发性肿瘤。只有少数研究调查了传播的RMS表型(n=16,13.6%)。RMS模型的利用领域包括测试药物(n=64,54.2%),研究肿瘤发生(n=56,47.5%),肿瘤建模(n=19,16.1%),成像(n=9,7.6%),放射治疗(n=6,5.1%),与放疗相关的长期影响(n=3,2.5%),并调查生物标志物(n=1,0.8%)。值得注意的是,没有集中于手术的临床前研究。
■这一最新综述强调了对具有来自原发性未治疗肿瘤的播散表型和细胞系的小鼠模型的需求。此外,应努力针对未充分开发的领域,如手术,放射治疗,和生物标志物。
UNASSIGNED: Rhabdomyosarcoma (
RMS) is the most common pediatric soft-tissue malignancy, characterized by high clinicalopathological and molecular heterogeneity. Preclinical in vivo models are essential for advancing our understanding of
RMS oncobiology and developing novel treatment strategies. However, the diversity of scholarly data on preclinical RMS studies may challenge scientists and clinicians. Hence, we performed a systematic literature survey of contemporary RMS mouse models to characterize their phenotypes and assess their translational relevance.
UNASSIGNED: We identified papers published between 01/07/2018 and 01/07/2023 by searching PubMed and Web of Science databases.
UNASSIGNED: Out of 713 records screened, 118 studies (26.9%) were included in the qualitative synthesis. Cell line-derived xenografts (CDX) were the most commonly utilized (n = 75, 63.6%), followed by patient-derived xenografts (PDX) and syngeneic models, each accounting for 11.9% (n = 14), and genetically engineered mouse models (GEMM) (n = 7, 5.9%). Combinations of different model categories were reported in 5.9% (n = 7) of studies. One study employed a virus-induced
RMS model. Overall, 40.0% (n = 30) of the studies utilizing CDX models established alveolar RMS (aRMS), while 38.7% (n = 29) were embryonal phenotypes (eRMS). There were 20.0% (n = 15) of studies that involved a combination of both aRMS and eRMS subtypes. In one study (1.3%), the
RMS phenotype was spindle cell/sclerosing. Subcutaneous xenografts (n = 66, 55.9%) were more frequently used compared to orthotopic models (n = 29, 24.6%). Notably, none of the employed cell lines were derived from primary untreated tumors. Only a minority of studies investigated disseminated
RMS phenotypes (n = 16, 13.6%). The utilization areas of RMS models included testing drugs (n = 64, 54.2%), studying tumorigenesis (n = 56, 47.5%), tumor modeling (n = 19, 16.1%), imaging (n = 9, 7.6%), radiotherapy (n = 6, 5.1%), long-term effects related to radiotherapy (n = 3, 2.5%), and investigating biomarkers (n = 1, 0.8%). Notably, no preclinical studies focused on surgery.
UNASSIGNED: This up-to-date review highlights the need for mouse models with dissemination phenotypes and cell lines from primary untreated tumors. Furthermore, efforts should be directed towards underexplored areas such as surgery, radiotherapy, and biomarkers.