FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor)

After evaluation, he was found to have a rare diagnosis of ALES in this age group, specifically with this Ewing Sarcoma RNA binding protein 1 and nuclear factor of activated T cells cytoplasmic 2 (EWSR1::NFATC2) gene fusion. This case highlights the challenges of diagnosing and the multidisciplinary management of rare variants of ES with uncommon gene fusions and raises awareness for the future potential of molecular diagnostics and treatment-specific applications for improved access to care and better outcomes for this population.

Finally, siRNA-mediated downregulation of PFKL resulted in elevated glucose levels, suppressed expression of IRF6 and NKX2-4, and activated FLI1. Thus, we connected an oncogenic regulatory network with deregulated glycolytic enzymes and glucose metabolism, thereby establishing a new in vitro model to develop novel therapeutic avenues in AML subsets.

Surgical resection and cervicothoracic fixation were performed, followed by radiotherapy (30 Gy/10 fractions) and Ewing-based chemotherapy (doxorubicin/ifosfamide). Local recurrence occurred despite multimodal therapy. This case highlights the clinical and diagnostic challenges associated with EWSR1-rearranged non-ETS sarcomas, which exhibit distinct molecular behaviors, morphology, and treatment responses compared to classical Ewing sarcoma.

The patient received six cycles of vincristine-doxorubicin-cyclophosphamide alternating with ifosfamide-etoposide, followed by partial amputation of the distal phalanx with clear margins. Ewing sarcoma of the great toe is exceptionally rare but can be successfully treated when identified early and managed with coordinated multimodal therapy. Clinicians should maintain vigilance for malignancy in non-healing digital lesions to ensure timely intervention and durable outcomes.

Multiple rare thyroid malignancies may present indistinguishably from ATC, emphasizing the need for meticulous histopathologic and molecular evaluation.

Intracranial EWS is exceptionally rare and poses a significant diagnostic challenge due to its nonspecific radiological features. Definitive diagnosis relies on integrated pathological and molecular genetic testing. This case underscores that a multimodal treatment strategy centered on maximal safe surgical resection, combined with radiotherapy and chemotherapy, can achieve favorable short-term oncological outcomes. A review of the literature highlights the prognostic importance of tumor location and extent of resection.

In this issue of Immunity, Ji et al. reveal that nutrient stress induces FLI1-mediated repression of pro-survival unfolded protein response programs, disrupting proteostasis and limiting NK cell persistence and function within tumors.

The compensatory ATR signaling axis acts as a collateral dependency and therapeutic target in patient-derived xenograft models of multiple FET rearranged cancers. In summary, these findings describe how oncogenes can disrupt physiologic DNA repair and provide the preclinical rationale for testing ATR inhibitors in FET rearranged cancers as part of ongoing early phase clinical trials.

We further compare EWSR1 with conventional antifibrotic approaches, outline research gaps, and propose directions for translational development. By positioning EWSR1 as a novel molecular node in fibrogenesis, this article underscores its promise as a next-generation therapeutic target for halting or reversing liver fibrosis.

Pharmacological inhibition of PI3K effectively counteracted the oncogenic effects mediated by SPTBN2 in both in vitro and in vivo models. These findings establish SPTBN2 as a novel oncoprotein and prognostic biomarker in BLCA, and highlight the SPTBN2-FLI1-PI3K/AKT axis as a promising therapeutic target for intervention.

show that the E26 transformation-specific (ETS) transcription factors ETS-related gene (Erg) and Friend leukemia integration 1 (Fli1) cooperatively maintain adult LEC homeostasis by sustaining transcriptionally distinct LEC populations, vascular integrity, immune-vascular interactions, and repression of proinflammatory and prothrombotic gene programs. These findings extend the known roles of Erg and Fli1 beyond the blood endothelium and provide mechanistic insight into human lymphatic disease associated with Erg haploinsufficiency.

These findings highlight an unexpected tumor-suppressive role for cIAP1 in fusion-driven sarcomas, contrasting with its pro-survival function in other cancers. Collectively, our results identify cIAP1 as a prognostically relevant, EWSR1::FLI1-regulated hub whose re-expression disrupts tumor progression, offering a potential therapeutic strategy to restore tumor-suppressive pathways in EwS.