Loss of Chromosome 3q Is a Prognostic Marker in Fusion-Negative Rhabdomyosarcoma

Dehner, Carina A.; Bell, Robert C.; Cao, Yang; He, Kevin; Chrisinger, John S.A.; Armstrong, Amy E.; Yohe, Marielle; Shern, Jack; Hirbe, Angela C.

doi:10.1200/po.23.00037

Cited by 3 publications

(1 citation statement)

References 22 publications

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“…Recently, significant progress was made in understanding the genetic and epigenetic factors associated with RMS (12). Numerous studies on RMS have identified new diagnostic and prognostic markers that have led to the development of novel therapeutic strategies (13). ROS have been identified as significant targets in highthroughput drug-screening assays (2).…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin Reductase Inhibitor Suppresses the Local Progression of Rhabdomyosarcoma With PDX Models

KINOSHITA,

KAMODA

et al. 2024

Cancer Genomics Proteomics

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Background/Aim: Chemoresistance in rhabdomyosarcoma (RMS) is associated with poor survival, necessitating the development of novel anticancer drugs. Auranofin (AUR), an anti-rheumatic drug, is a thioredoxin reductase (TXNRD) inhibitor with anticancer properties. Although patient-derived xenograft (PDX) models are essential for studying cancer biology, reports on sarcomas using the PDX model are scarce because of their rarity. This study aimed to investigate the effectiveness of AUR treatment in RMS using a PDX model to evaluate its impact on local progression. Materials and Methods: A 20-year-old woman who was diagnosed with alveolar RMS was used to generate the PDX model. RMS PDX tumors were implanted in nude mice and divided into non-treated (vehicle) and treated (AUR) groups. Tumor volume and weight were evaluated, and immunohistochemical staining was performed to evaluate local progression of the sarcoma. The relationship between the TXNRD-1 expression and survival probability of patients with RMS was evaluated using publicly available expression cohorts. Results: AUR significantly suppressed RMS tumor progression over time. It also significantly suppressed the tumor size and weight at the time of excision. Histological evaluation showed that AUR induced oxidative stress in the PDX mouse models and inhibited the local progression of RMS by inducing apoptosis. High TXNRD-1 expression was found to be a negative prognostic factor for overall survival in patients with RMS. Conclusion: AURinduced inhibition of TXNRDs can significantly impede the local progression of RMS through the oxidative stressapoptosis pathway as demonstrated in PDX models. Thus, targeting TXNRD inhibition may be a promising therapeutic strategy for the treatment of RMS.

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Section: Discussionmentioning

confidence: 99%

Thioredoxin Reductase Inhibitor Suppresses the Local Progression of Rhabdomyosarcoma With PDX Models

KINOSHITA,

KAMODA

et al. 2024

Cancer Genomics Proteomics

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Role of CD73 and the purinergic signaling pathway in the pathogenesis of fusion-negative rhabdomyosarcoma

Fascì,

Deaglio

2024

Purinergic Signalling

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Classification of pediatric soft and bone sarcomas using DNA methylation-based profiling

Silva,

Euzébio,

Ruas

et al. 2024

BMC Cancer

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Loss of Chromosome 3q Is a Prognostic Marker in Fusion-Negative Rhabdomyosarcoma

Abstract: We show that loss of chr3q is associated with worse outcomes in fusion-negative (FN)-RMS compared with fusion-positive (FP)-RMS, suggesting that this chromosomal abnormality could be a prognostic marker for (FN) RMS.

Cited by 3 publications

References 22 publications

Thioredoxin Reductase Inhibitor Suppresses the Local Progression of Rhabdomyosarcoma With PDX Models

Thioredoxin Reductase Inhibitor Suppresses the Local Progression of Rhabdomyosarcoma With PDX Models

Role of CD73 and the purinergic signaling pathway in the pathogenesis of fusion-negative rhabdomyosarcoma

Classification of pediatric soft and bone sarcomas using DNA methylation-based profiling

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