Rhabdomyosarcoma

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.

Despite multimodal therapy, all patients progressed (median EFS 16.5 months), with poorest outcomes in older children (Cases 1,3,4). BCOR mutations may define an aggressive RMS subtype in pediatric group.

DICER1 mutations are frequently detected in pediatric PPB, CN, SCST, ASK, nodular thyroid goiter, thyroid adenoma, and genitourinary rhabdomyosarcoma, which often represent as the index case of DICER1 syndrome. Performing DICER1 mutation testing in these patients not only facilitates tumor diagnosis and secondary cancer surveillance, but also enables the comprehensive genetic risk assessment and management for patient's family members.

Leveraging the observed sensitivity of muscle cells to atorvastatin in clinical settings and utilizing untargeted metabolomic analysis of atorvastatin-treated RD rhabdomyosarcoma cells, we identified reduced levels of aminoadipic acid, an intermediate in lysine catabolism...However, we demonstrated that it is catabolically cleaved to p-nitroanilide, with this molecule driving the cytotoxic activity observed in our experiments. Although lysine metabolism was not fully suppressed by lysine-p-nitroanilide, these findings provide valuable insights for developing novel therapies for rhabdomyosarcoma.

Here, we show that sotorasib, adagrasib, and the RAS-ON inhibitor RMC-6291 are effective in a neuroblastoma cell line altered by KRAS(G12C). Importantly, sotorasib also decreased ERK phosphorylation in a NRAS(G12C)-altered cell line xenograft model; however, this treatment did not prolong survival as a single agent. These results suggest that combinations of targeted agents that include sotorasib may be required for clinical benefit in pediatric patients with H- or NRAS(G12C)-altered malignancies in addition to those with KRAS(G12C)-altered malignancies.

Notably, the presence of cartilage foci within a RMS-like neoplasm represents a strong clue to an underlining DICER1 alteration. The rarity of this presentation in the nasal fossa at this age, coupled with its implications for diagnosis, treatment, and familial screening, emphasizes the need for awareness of the morphology patterns of DICER1-associated neoplasms across diverse anatomical sites.

P1/2, N=90, Recruiting, St. Jude Children's Research Hospital | Active, not recruiting --> Recruiting | N=46 --> 90