Rhabdomyosarcoma

This MYOD1 mutant cohort demonstrates increased MYOD and reduced MYF4 immunostaining, high risk of local failure and poor survival in agreement with other studies. Increased treatment intensity and improved local control should be considered for these patients.

Here, We report a case of paratesticular alveolar rhabdomyosarcoma in an adult patient who initially complained of increased scrotal volume for two years and presented with a PAX3-FOXO1 fusion. This emphasizes the dire prognosis of the disease, reinforcing the need for thorough and directed diagnostic efforts.

Our findings indicated that tyrosine kinase receptors are upregulated in NRSTS and exhibited a distinct expression pattern within various subgroups. High expression of VEGFR2 and PDGFRα significantly correlated with reduced survival and may guide targeted therapy approaches for this poor prognosis group of patients.

P2, N=202, Active, not recruiting, St. Jude Children's Research Hospital | Trial completion date: Oct 2024 --> Oct 2029

P2, N=100, Not yet recruiting, Fudan University

P2, N=100, Not yet recruiting, Fudan University

P3, N=118, Recruiting, Children's Oncology Group | Active, not recruiting --> Recruiting

P1, N=22, Recruiting, University of Wisconsin, Madison | Suspended --> Recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

This study shows that ASAP1 and ARF1 are necessary for myogenic differentiation, providing a deeper understanding of differentiation in FN-RMS and illuminating an opportunity to advance differentiation therapy. Implications: ASAP1 and ARF1 regulate MEKi-induced differentiation of FN-RMS cells by modulating WWTR1 (TAZ) activity, supporting YAP1/TAZ inhibition as a FN-RMS differentiation therapy strategy.

P2, N=65, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2024 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Oct 2025

P3, N=40, Recruiting, N.N. Petrov National Medical Research Center of Oncology

P2, N=23, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

These transplantable FA mouse tumor cell lines should be valuable for testing effects of new radiation therapy protocols including FLASH high dose rate radiation delivery, immunotherapies, and combined radiation and chemotherapy treatments for radiosensitive FA patients.

P=N/A, N=400, Recruiting, Eastern Cooperative Oncology Group | Trial completion date: Nov 2024 --> May 2027 | Trial primary completion date: Nov 2024 --> May 2027

The efficacy and feasibility of Hippo pathway-related drugs for targeted therapy of musculoskeletal diseases are also discussed in our study. These endeavors offer novel insights into the application of Hippo signaling in musculoskeletal disorders, providing effective therapeutic targets and potential drug candidates for treating such conditions.

P1/2, N=64, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

We additionally show that, in some FP-RMS, KDM3A also increases PAX3-FOXO1 levels. Together, our studies illuminate mechanisms of action of the KDM3A/ETS1 regulatory module, and reveal novel targetable mechanisms of PAX3-FOXO1 chromatin complex regulation, in FP-RMS.

Primary gastric ARMS is an extremely rare condition. Better awareness of this entity and its similarity to NEC is necessary for appropriate diagnosis and treatment.

P2, N=4, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

Due to its non-specific presenting symptoms, prostate ERMS can be easily misdiagnosed, which can lead to treatment delay. Multimodality approaches, including neoadjuvant/adjuvant chemotherapy, radiotherapy, and radical resection, can improve the survival rate and reduce ERMS patient mortality.

P1/2, N=114, Recruiting, Milton S. Hershey Medical Center | Not yet recruiting --> Recruiting

Histological and immunohistochemical features supported the diagnosis of metastatic cardiac embryonal RBM spindle cell variant in the cat. Cardiac embryonal RBMs should be included in the differential diagnosis of cardiac and thoracic neoplasms in domestic cats presenting with clinical signs indicative of cardiac arrest or sudden death.

The undifferentiated epithelioid morphology and unusual aberrant neuroendocrine marker expression posed significant diagnostic challenges. The major differential diagnoses were discussed in this report.

P1, N=22, Suspended, University of Wisconsin, Madison | Recruiting --> Suspended

Niclosamide, piroctone olamine, and pyrvinium pamoate are promising, cost-effective therapeutic agents for the treatment of TBX2/TBX3-dependent cancers.

A cohort of these CAD gene targets are also conserved in early differentiating T cells and include genes that spur leukemia/lymphoma translocations. Our results suggest the CAD targeting of translocation prone oncogenic genes is non-pathologic biology and aligns with initiation of cell fate transitions.

We identified miR-335-5p as significantly upregulated in plasma derived EVs and tumor tissue of patients affected by ARMS. Its expression correlates to stage and survival in patients. Future studies are needed to validate miR-335-5p as prognostic biomarker and to deeply elucidate its biological role.

P2, N=9, Active, not recruiting, National Cancer Institute (NCI) | N=49 --> 9 | Trial completion date: Sep 2024 --> Oct 2025

DUX4 IHC is a highly sensitive and specific surrogate marker for the presence of CIC::DUX4 fusion, demonstrating its utility in establishing a diagnosis of CRS.

Our study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy.

Combined treatment with surgery and HDR brachytherapy is feasible in very young children with (P)RMS and leads to a favorable oncologic outcome. Preliminary data show a good functional preservation.

The cisplatin- and doxorubicin-based HIPEC significantly reduces peritoneal tumor dissemination in vivo. Further investigations are needed to explore the underlying molecular responses to optimize therapeutic strategies.

In patients with at least one mutation in BCOR, NF1, TP53, KRAS, HRAS, or CTNNB1, later age of onset is associated with poorer prognosis. In patients with mutations only in tumor suppressor genes BCOR or NF1, later age of onset is associated with poorer prognosis.

P1/2, N=27, Not yet recruiting, University of Florida

P1/2, N=21, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

There was a greater reduction in tumor volume in alveolar versus nonalveolar RMS. Early tumor volume reduction was associated with OS and local failure in embryonal or spindle cell/sclerosing RMS, all of which were confirmed FOXO1 fusion negative and had higher incidence of local compared with distant failures.

Serratia marcescens prodigiosin showed cytotoxic effects on cancer cells and boosted IL-10 and IL-4 serum levels, acting as an immunomodulator.

Our study identifies a novel role for nuclear PLCδ4 as a regulator of cyclin B1 via Akt-dependent phosphorylation. The modulation of PLCδ4 expression and its downstream targets could represent a crucial signaling pathway to block embryonal RMS cell proliferation.

No abstract available

Further studies showed that RMS PDCs retained the genetic alterations and the expression of RMS hallmark and dependency genes in matched primary tumors and acted as valuable tools to assess drug responses and pharmacogenomic interactions. Our study provides unique PDCs that are available for preclinical studies of RMS and further advances the feasibility of RMS PDCs as valuable tools for developing personalized treatments for patients.

P=N/A, N=60, Recruiting, Mayo Clinic | N=180 --> 60

The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC.