Rhabdomyosarcoma

Additionally, we examine immunotherapeutic strategies, epigenetic modifiers, and noncoding RNAs as potential therapeutic avenues. Together, these insights provide a comprehensive framework for developing biomarker-guided, multi-targeted therapies to improve outcomes in ARMS.

P2, N=59, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Feb 2025 --> Nov 2025

In embryonal RMS and PAX3/7::FOXO1 fusion-negative RMS, individuals with South Asian or Asian-Pacific Islander ancestry showed worse EFS (HR: 2.06; 95% CI: 1.07-3.97; p = 0.03 and HR: 2.01; 95% CI: 1.07 - 3.76; p = 0.03, respectively) and OS (HR: 2.30; 95% CI: 1.09-4.84; p = 0.03 and HR: 2.33; 95% CI: 1.15 - 4.70; p = 0.020, respectively) compared to those with primarily European genetic ancestry. These findings suggest that genetic ancestry influences survival outcomes within RMS subtypes, and further understanding may improve precision medicine-based efforts.

P1, N=65, Recruiting, Florida International University | Phase classification: P --> P1

Patients with MYOD1 mutations have an extremely poor prognosis, which is independent of clinical staging and grading. MYOD1 mutation detection in rhabdomyosarcoma has significant value for auxiliary diagnosis and prognostic assessment.

Thus, immunostaining for CD138, CK, desmin, vimentin, S-100, and HMB45 were requested and the results were compatible with the final diagnosis of amelanotic plasma melanoma. It is crucial to consider melanoma as one of the differential diagnoses of a tumor with plasmacytoid feature and CD138 positive staining as it can mimic multiple myeloma as demonstrated in this case report.

Initially misdiagnosed as rhabdomyosarcoma, the diagnosis of EES was ultimately confirmed via RNA sequencing revealing the EWSR1-FLI1 fusion gene. She underwent neoadjuvant chemotherapy followed by radical resection of the tumor.

We found no genetic differences between implant-associated and non-implant-associated rhabdomyosarcomas. Further investigation is needed to understand the contribution of metallic implants to tumorigenesis. Physicians should be aware of this diagnosis when a new mass arises in a patient with long-standing orthopaedic implants.

Whereas intermediate PAX3::FOXO1 expression maximizes chromatin binding to modulate gene expression, high PAX3::FOXO1 expression alters S phase progression and increases accessibility behind the replication fork. We conclude that PAX3::FOXO1 exerts dosage-dependent functions to influence epigenetic heterogeneity in fusion-positive rhabdomyosarcoma.

P2, N=28, Not yet recruiting, Shandong First Medical University Affiliated Cancer Hospital; Shandong First Medical University Affiliated Cancer Hospital

MRTKIs regorafenib and infigratinib were used at a concentration of 0.1uM added to the fish water 4 hours post cell inoculation. We have developed an embryonic zebrafish xenograft model of RMS, which allows assessment of tumour growth, vascularisation initiation and therapeutic responses to clinically relevant MRTKIs. The identification of VEGF-A secretion as potential biomarker for Regorafenib response and the separation of therapeutic effects on tumour growth and neovascularisation suggests additional value of our model for response prediction to MRTKIs.

Our study reveals a novel EHMT1-SOX8 axis that mediates metastasis in ERMS.

By demonstrating that PRL-3 enhances cancer progression independently of its catalytic activity, this study shifts focus toward targeting its binding functions as a therapeutic strategy. This study demonstrates that PRL-3 drives cancer initiation and progression through a phosphatase-independent mechanism across diverse models, highlighting the need to therapeutically target its non-catalytic protein interactions in future cancer treatment strategies.

In summary, CD140b is a sensitive but imperfectly specific marker for AFX and PDS. Several targeted drugs have shown efficacy in PDGFR-expressing tumors, and our findings further delineate therapeutic strategies for a selected group of poorly differentiated cutaneous neoplasms.

We show that in hRMS ephrin-A5 binds and signals to EphA8 and EphA7 binds and signals to ephrin-A2, and that Fc chimeras of both molecules are potent inhibitors of hRMS proliferation. These results identify key differences between hRMS and normal muscle cells and support further research into Eph: ephrin signaling as potential differentiation therapies.

A subset of five cases were stained for PAX7, and a single case of malignant OFMT showed weak expression. To our knowledge, this is the first formal study of rhabdomyoblastic marker expression in OFMT.

Next-generation sequencing revealed a MEIS1::NCOA1 fusion without additional genetic alterations. She presented with extensive local disease throughout the abdomen, while the uterus and adnexa appeared normal intraoperatively.

Both tumors were classified as malignant teratoid medulloepithelioma with rhabdomyosarcomatous differentiation. Intraocular medulloepithelioma may contain areas with rhabdomyosarcomatous differentiation and have DICER1 mutations.

Histopathologic findings showed spindle and rhabdoid cells with positive immunoreactivity to Desmin, myogenin and myoD1. In conclusion, it is crucial to differentiate rhabdomyosarcoma from other more common intraosseous malignancies, and using Desmin staining as part of the initial immunohistochemical panel can aid in the diagnosis process.

P2, N=135, Recruiting, St. Jude Children's Research Hospital | Phase classification: P1/2 --> P2 | N=100 --> 135

Targeted medical therapy is indicated and shown to be effective for the treatment of benign cardiac tumours causing significant rhythm or mass effect. mTOR inhibitors should be considered in the treatment of rhabdomyomas and beta blockade for haemangiomas.

Our literature review demonstrates that within the 248 cases, which include three intracranial DICER1-mutated neoplasias and one reference group, most somatic mutations accumulate in the RNase IIIb domain, while germline mutations are usually evenly distributed throughout the gene. Overall, further research is necessary to unravel the cell-of-origin of the respective tumor types and whether other, hitherto undescribed, genetic factors may contribute to the development of ETMR and DICER1-associated intracranial sarcomas.

TFCP2 fusion sarcomas are proven to be aggressive and have poor prognosis. Additional work is needed to define the optimal treatment course for TFCP2 fusion sarcomas.

P2, N=1376, Active, not recruiting, National Cancer Institute (NCI) | N=2316 --> 1376 | Trial completion date: Jun 2025 --> May 2026 | Trial primary completion date: Jun 2025 --> Mar 2025

Despite the small sample size, these findings suggest potential age-related molecular mechanisms and highlight candidate genes for further investigation as novel therapeutic targets. Notably, we identified CDK9 as a promising target, warranting further exploration in the context of ARMS treatment.

We show that small-molecule EP300 inhibition can suppress fusion protein-induced oncogenic transformation both in vitro and in vivo in mouse models. Overall, our study reveals a molecular basis for VGLL involvement in cancer and provides a framework for targeting tumors carrying VGLL, TEAD, or NCOA translocations.

Mechanistically, the inhibition of ROCK and FAK resulted in fewer focal adhesions, thereby facilitating increased cell velocity. These findings suggest that targeting specific signalling pathways can effectively modulate migration and survival of metastatic RMS559 cells.

P=N/A, N=213, Completed, Children's Oncology Group | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025

Mutations were investigated in 22 cases, all of which returned negative results. In summary, canine STSs variably expressed CD117, which suggests that tyrosine kinase inhibitors may represent a promising targeted therapy for selected canine STSs histotypes.

Evidence of neural differentiation in ES unravels interesting hints about its controversial histogenesis. Furthermore, awareness of this event must be increased to avoid misdiagnosis with neuroblastoma, which shows significant morphological overlap.

Moreover, the aberrant expression of DLX5 in PAX3-FOXO1-driven RMS was regulated by KDM4B/H3K9me2 axis. These findings provided potential therapeutic targets for RMS treatment.

P1, N=24, Recruiting, Baylor College of Medicine | Trial primary completion date: Feb 2025 --> Oct 2025

P2, N=88, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting

This study uses functional modeling and omics approaches to identify IGFBP5 as a candidate mediator of anti-tumor growth mechanisms originating from tumor-neighboring mesenchymal stromal cells. Tumors of mesenchymal origin, such as RMS, are known for their heterogeneity, and this could potentially pose a limitation to the study. However, a clinical relevance is emphasized by consistent findings across patient cohorts. These insights pave the way for novel therapeutic strategies modulating activities of stromal cell subsets at primary and metastatic sites in RMS.

Since these neoplasms are rare and particularly occur in the pediatric population, pathologists should be aware of the potential relationship of these tumors with an underlying DICER1 syndrome in order to perform or suggest additional molecular pathologic analysis and refer patients and their parents for genetic counseling and testing. This review describes the various DICER1-related tumor types with emphasis on the histological features, reflects on the molecular pathogenesis of DICER1, and aims to raise awareness of this syndrome to facilitate earlier diagnosis.

Similarly, weak predominantly patchy staining was seen in half (40/80) of other non-Hodgkin lymphomas and sporadically in embryonal rhabdomyosarcoma, Merkel cell carcinoma, small cell lung carcinoma, and Wilms tumor. Thus, diffuse and strong PKC β II immunoreactivity appears to be a reliable diagnostic marker for distinguishing classic Ewing sarcoma from histologic mimics.

P=N/A, N=20, Recruiting, Lille University

These findings highlight the prognostic value of systemic inflammatory markers in pediatric STS, emphasizing their potential to refine risk assessment and guide treatment.

Apoptosis, or programmed cell death, plays a critical role in maintaining tissue homeostasis by eliminating damaged or abnormal cells. Additionally, interactions were observed from combinations of the apoptosis pathway targeted agents with other agents, including PARP inhibitors, the XPO1 inhibitor eltanexor, and the PI3K inhibitor copanlisib. Enhanced activity was also observed from combinations of the apoptosis pathway targeted agents with MAPK pathway targeted agents, including the MEK inhibitor cobimetinib as well as adagrasib and MRTX1133, which specifically target the KRAS G12C and G12D variants, respectively.

In contrast, high PSMA expression was seen in only 0-40% of the non-neoplastic vessels in vascular tumors, while 8% of them expressed PSMA in the tumor cells. Thus, with variable frequency among the different subtypes, a subset of bone and soft tissue tumors, both malignant and intermediate behavior, express PSMA and these patients may benefit from PSMA-targeting PET/CT scans or PSMA targeted radioligand therapy.

Prognosis correlated with high-risk morphologic features in the adenosarcomatous component, including sarcomatous overgrowth, extensive rhabdomyosarcomatous differentiation, vascular invasion, and high-grade nuclear atypia. "Mixed endometrioid adenocarcinoma and adenosarcoma" is a clonal biphasic malignant neoplasm of uncertain histogenesis, with a high frequency of DICER1 mutations.

On ARST1431, tumors >5cm at diagnosis had poor local control despite dose escalation to 59.4 Gy. Proton and photon RT had equivalent local control. For select patients, DPE significantly improved local control.