Ewing Sarcoma

Understanding the complex immune evasion machinery driven by Gal-9 expressing leukemic cells will enable the identification of novel therapeutic strategies for efficient immunotherapy in leukemic patients. Combined treatment approaches targeting T-cell immunoglobulin and mucin domain-3 (Tim-3)/Gal-9 and other immune checkpoint pathways can be considered, which may enhance the efficacy of host effector cells to attack leukemic cells.

P2, N=59, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2024 --> Jan 2024

P2, N=31, Active, not recruiting, Sarcoma Oncology Research Center, LLC | Trial completion date: Oct 2023 --> Mar 2025 | Trial primary completion date: Jan 2023 --> Dec 2024

P2, N=5, Active, not recruiting, National Cancer Institute (NCI) | N=49 --> 5 | Trial completion date: Sep 2027 --> Apr 2025 | Trial primary completion date: Sep 2027 --> Mar 2024

P2, N=109, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2023 --> Sep 2024

This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

This case highlights the nonspecific nature of DSRCT symptoms. In clinical practice, it is crucial to meticulously evaluate unexplained intestinal obstruction in young patients, considering DSRCT as a differential diagnosis to avoid delays in diagnosis.

P1, N=44, Recruiting, Seattle Children's Hospital | Trial completion date: Jun 2038 --> Jun 2040 | Trial primary completion date: Jun 2024 --> Jun 2025

Critically, these findings have clinical relevance as TNS3 expression in EWS tumors positively correlates with that of ETS1. Implications: ETS1's transcriptional regulation of the gene encoding the focal adhesion protein TENSIN3 in Ewing sarcoma cells promotes cell movement, a critical step in the evolution of metastasis.

The differentiation of the ES from other small cell tumors may be difficult and requires awareness for histological and immunohistochemical features. It should be kept in mind that the diagnosis can be challenging due to uncommon locations and radiological misinterpreted.

P=N/A, N=186, Completed, Giselle Sholler | Active, not recruiting --> Completed | Trial completion date: Jun 2026 --> Jan 2024 | Trial primary completion date: Jun 2025 --> Jan 2024

P2, N=30, Recruiting, Shanghai Pharmaceuticals Holding Co., Ltd | Not yet recruiting --> Recruiting

A better understanding of the current status and prospects of immunotherapy for BM is crucial for the rationale selection of appropriate BM patients for immunotherapy. This study is expected to help clinical physicians and researchers gain comprehensive insights into the developmental trends of BM immunotherapy, providing practical guidance for the application of immunotherapy in BM patients.

P1, N=44, Recruiting, Peking University People's Hospital

Our results show that fusion testing can be a helpful diagnostic tool, especially in cases with unusual or uncommon morphology in superficial sites. Furthermore, it can allow for the identification of potential therapeutic targets in some instances.

These studies are the first to demonstrate the role of human immune effector cells in anti-CD99-mediated Ewing tumor death. We propose that the engagement of CD99 by NOA2 results in the recruitment of intratumoral macrophages. In addition, interruption of the CD99:PILRα checkpoint axis may be a relevant therapeutic approach to activate tumor-associated macrophages.

Hence, aberrantly expressed ETS proteins derepress pericentromeric heterochromatin, yielding pathogenic RNAs which transmit genotoxic stress and inflammation to local and distant sites. Monitoring HSAT2,3 plasma levels and preventing their dissemination may thus improve therapeutic strategies and blood-based diagnostics.

Our data suggests that the Zinc-finger domain (ZnF) with flanking arginine and glycine rich (RGG) domains provide high affinity binding, while the RNA recognition motif (RRM) with its RGG domains offer improved specificity. This model offers a rational for EWSR1 specificity to encompass a wide range in contexts due to the DNA forks always found with R-loops.

These data exploit EWS-FLI1 driven alterations in cell context to broaden the therapeutic window of berzosertib and cisplatin to establish a promising combination therapy and a novel in vivo schedule.

These neoplasms are considered to be synchronous due to the presentation of each entity within 6 months. Considering the aggregate yearly incidence of Ewing sarcoma (approximately 1 case per 750 000 per year) and LGCOS (approximately 1 case per 10 million per year), the aggregate yearly probability of developing both of these genetically unrelated tumors in a single individual is 1 per 7.5 trillion per year, and it is likely such an event has never happened in the past.

P1, N=25, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024

P2, N=24, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

MD simulations revealed that the tyrosine-rich termini exhibit compact conformations with unique contact networks and provided critical input on the relationship between contacts formed within a single molecule (intramolecular) and inside the condensed phase (intermolecular). These findings enhance our understanding of FET proteins' condensate-forming capabilities and underline differences between EWS, FUS, and TAF15.

In our study, the Signatera ctDNA assay was a reliable reflection, or even predictor, of relapse or progression in five pediatric patients with solid tumors. Further investigation is needed to validate the reliability and best utility of this test. This study was supported by the Natera early adopter program.

P1, N=74, Terminated, Sumitomo Pharma America, Inc. | Trial completion date: Oct 2024 --> Jan 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Jan 2024; Sponsor's decision to terminate further development of the program.

P2, N=15, Completed, Monica Thakar | Active, not recruiting --> Completed

This case highlights the successful management of an advanced PNET with neoadjuvant chemotherapy, pneumonectomy, and partial resection of the left atrium employing cardiopulmonary bypass. The patient remained disease-free after three years. Our analysis of surgically treated cases indicates that neoadjuvant chemotherapy can contribute to improved prognoses for PNET patients. It is crucial to emphasize that complete surgical excision remains the cornerstone of treatment, underscoring the importance of surgeons considering radical surgical approaches whenever feasible for patients with pulmonary PNETs.

From 2019 to 2022, 1387 patients with STS were registered in C-CAT. The histological types included leiomyosarcoma in 357 patients, dedifferentiated liposarcoma in 178 patients, and undifferentiated pleomorphic sarcoma in 82 patients, and the others. The most commonly altered genes included TP53, CDKN2A, Rb1, and CDKN2B.

Interestingly, in three cases there was emergence of a new variant activating the RAF/MAPK or AKT pathway.Conclusion Pediatric sarcomas display a range of genomic changes over time. Given the observed changes in oncogenic alterations, there may be utility to repeat sequencing of relapsed tumor biopsies to understand these changes.

PRR11 and mast cell infiltration are potential prognostic indicators in ES. PRR11 possibly affects the prognosis of patients with ES through the cell cycle pathway.

Because of its non-elevated serum PSA level, prostate SRCT is often ignored as a possibility of malignant tumor and regarded as benign prostatic hyperplasia (BPH). The possibility of prostate SRCT need to be considered if dysuria symptoms could not alleviate significantly after a period of oral treatment.

P=N/A, N=180, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P1/2, N=128, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting | N=184 --> 128

As a conclusion increased serum GDF11 levels in AML patients may be linked to the regeneration ability of leukemic stem cells. There is a need for studies investigating GDF11 expression in myeloblasts.

P=N/A, N=44, Completed, Masonic Cancer Center, University of Minnesota | Recruiting --> Completed | N=20 --> 44

Furthermore, the multi-gene RF classifier appeared advantageous over using high ETV4 expression alone, previously proposed as surrogate to identify CIC rearrangement. Taken together, the expression-based classifier can offer valuable support for SBRCS pathological diagnosis.

P1/2, N=184, Recruiting, Pfizer | Trial primary completion date: Feb 2024 --> Aug 2024 | Phase classification: P2 --> P1/2

Sarcoma panel Nanopore adaptive sampling can diagnose rare sarcoma types, such as FUS translocated Ewing's sarcoma, and aid in characterizing the molecular landscape. Furthermore, Nanopore analysis may facilitate blood-based tumor markers. Additional testing of a diverse sarcoma cohort is needed to evaluate the clinical utility of this approach.

The epigenetic regulatory mechanisms such as DNA methylation, histone modification and microRNAs can modulate the diverse effectors of signalling pathways and consequently the growth, differentiation and tumorigenicity of CSCs. In the end, we briefly discuss the therapeutic potential of targeting these epigenetic regulators and their target genes in CSCs.

Our study broadens the spectrum of tumors associated with EWSR1::CREM rearrangement and is the first to document its presence in SCCs of the lung and head and neck. While there is no specific standardized approach to treatment for patients whose tumors have these translocations, it is noteworthy that all three patients in this series are alive despite the presence of metastases and, in some instances, the absence of therapy over several years. Identification of additional cases will be helpful to better understand the disease course and optimal therapy of SCC harboring the EWSR1::CREM fusion.

P=N/A, N=600, Recruiting, Institut Curie | Trial primary completion date: Sep 2026 --> Apr 2027

P=N/A, N=213, Recruiting, Children's Oncology Group | Trial primary completion date: Dec 2023 --> Dec 2024