Oncogenic NRAS Accelerates Rhabdomyosarcoma Formation When Occurring within a Specific Time Frame during Tumor Development in Mice

Ragab, Nada; Bauer, Julia; Botermann, Dominik Simon; Uhmann, Anja; Hahn, Heidi

doi:10.3390/ijms222413377

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…Moreover, ectopic mouse models did not recapitulate any of the human anatomical tumor sites, thus having very limited translational value. While orthotopic mouse models recapitulated the limb RMS phenotype, a variety of additional tumor locations were observed merely in GEMM systems within our study cohort, including the abdomen, back, head/neck, rib cage, pelvis, body wall, and tongue (19,20,27,(64)(65)(66)(67)(68)(69)(70).…”

Section: From Bedside To Benchmentioning

confidence: 88%

“…Ragab el. showed that induction of the oncNRAS mutation in 2-week-old Ptch+/-NRasfl/+ mice (GEMM) accelerates eRMS formation compared to 4-week-old mice (68). The other studies utilized mice of different ages, including 3-week-old mice (86), mice between 4 to 8 weeks (87, 88), 6 to 8 weeks (41,89), or 8 to 12 weeks (90,91), irrespective of the mouse model subtype.…”

Section: Patient´s Agementioning

confidence: 99%

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Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside

Martynov,

Dhaka,

Wilke

et al. 2024

Front. Oncol.

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BackgroundRhabdomyosarcoma (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.MethodsWe identified papers published between 01/07/2018 and 01/07/2023 by searching PubMed and Web of Science databases.ResultsOut 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.ConclusionsThis 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.

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Section: From Bedside To Benchmentioning

confidence: 88%

Section: Patient´s Agementioning

confidence: 99%

Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside

Martynov,

Dhaka,

Wilke

et al. 2024

Front. Oncol.

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Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma

Gutierrez

Rytlewski

Scherer

et al. 2023

CIMB

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Rhabdomyosarcoma (RMS) is an aggressive form of cancer that accounts for half of all pediatric soft tissue sarcomas. Little progress has been made in improving survival outcomes over the past three decades. Mouse models of rhabdomyosarcoma are a critical component of translational research aimed at understanding tumor biology and developing new, improved therapies. Though several models exist, many common mutations found in human rhabdomyosarcoma tumors remain unmodeled and understudied. This study describes a new model of embryonal rhabdomyosarcoma driven by the loss of Nf1 and Ink4a/Arf, two mutations commonly found in patient tumors. We find that this new model is histologically similar to other previously-published rhabdomyosarcoma models, although it substantially differs in the time required for tumor onset and in tumor growth kinetics. We also observe unique sex-dependent phenotypes in both primary and newly-developed orthotopic syngeneic allograft tumors that are not present in previous models. Using in vitro and in vivo studies, we examined the response to vincristine, a component of the standard-of-care chemotherapy for RMS. The findings from this study provide valuable insight into a new mouse model of rhabdomyosarcoma that addresses an ongoing need for patient-relevant animal models to further translational research.

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Oncogenic NRAS Accelerates Rhabdomyosarcoma Formation When Occurring within a Specific Time Frame during Tumor Development in Mice

Cited by 2 publications

References 27 publications

Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside

Contemporary preclinical mouse models for pediatric rhabdomyosarcoma: from bedside to bench to bedside

Loss of Nf1 and Ink4a/Arf Are Associated with Sex-Dependent Growth Differences in a Mouse Model of Embryonal Rhabdomyosarcoma

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