Rhabdomyosarcoma

P2, N=115, Active, not recruiting, St. Jude Children's Research Hospital | Trial primary completion date: Dec 2025 --> Dec 2026

Knocking down YOD1 or inhibiting it by G5 could suppress FP-RMS growth both in vitro and in vivo, through promoting the degradation of both PAX-FOXO1 and N-Myc. Collectively, our results identify that YOD1 promotes RMS progression by regulating the PAX3-FOXO1-N-Myc positive feedback loop, and highlight YOD1 inhibition as a promising therapeutic strategy that concurrently reduces the levels of both oncogenic proteins.

P1, N=10, Not yet recruiting, University of Rochester | Initiation date: Jul 2025 --> Jan 2026

Our study demonstrates that the majority (86%) of SLCTs with heterologous RMS harbor double DICER1 mutations (a hotspot mutation and a nonsense or frameshift loss-of-function mutation), supporting the existing knowledge on DICER1 mutations associated with RMS heterologous elements, the presence of which should trigger genetic counselling. Our findings also suggest that molecular alterations other than DICER1, namely, TERT promoter and TP53 mutations, may contribute to component-specific oncogenic transformation.

These findings indicate that FGF8 exerts oncogenic effects in FP-RMS via FGFR4 and may exert oncogenic effects in P3F-independent relapses via FGFR1. Our study reveals the functional significance of FGF8 in FP-RMS and provides a rationale for preclinical studies of FGFR inhibitors in FP-RMS.

Under specific circumstances, CNB can provide an effective diagnostic approach for thyroid tumors. Moreover, in this case, we identified a novel TP53 intronic mutation that may drive the development of thyroid PRMS.

These data identify tolerated dose levels for a novel, intravenously delivered STING agonist compound that results in on-target effects in systemic and intratumoral immune responses in dogs with solid tumors.

Collectively, these findings demonstrate that distinct miRNA profiles can differentiate pediatric sarcoma types and subtypes and offer clinically relevant insights into tumor biology, prognosis, and potential diagnostic application.

The cytotoxic T cells in pRMS bear markers of exhaustion (LAG3, HAVCR2, EOMES), and the macrophages express myeloid checkpoint-related genes (SIGLEC1, SIRPA, CSF1R, HAVCR2). This transcriptomic data suggests that targeting MIF and APP signaling in pRMS may have therapeutic potential; however, studies on multiple-patient cohorts, protein verification, and in vitro and in vivo validation are still needed for clinical actionability.

Olaparib and temozolomide (OT) combination therapy is in clinical trial evaluation for rhabdomyosarcoma (RMS). The combination of OT + alpelisib also kills RMS cells which are resistant to standard-of-care combination chemotherapy and was effective in preclinical xenograft mouse models at curbing tumor growth. Our work defines a common resistance pathway in RMS and has credentialled PIK3CA/AKT inhibition as a preclinical strategy to kill therapy resistant RMS.

These cases expand the landscape of FOXO1-rearranged neoplasms and describe a potential new uterine mesenchymal entity. Further study of additional cases is needed to establish whether these rearrangements truly represent an initiating event for a distinct subset of uterine sarcomas, or whether FOXO1 rearrangements simply represent an additional noninitiating/nondriver event within other established tumor types.

We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.