Uterine Cancer

P2, N=23, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Nov 2026

P1/2, N=54, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Sep 2026 --> Jul 2027

This case underscores the diagnostic complexity of TFE3-rearranged PEComas, which can lack smooth muscle marker expression and mimic other high-grade uterine malignancies. Recognition of the nested vascular arrangement and utilization of melanocytic and TFE3 markers are key for diagnosis.

This finding suggests that BRCA1-associated USC may be sensitive to poly ADP-ribose polymerase inhibitors, and also raises the question of whether risk-reducing hysterectomy should be considered for patients with BRCA1 mutation. USC with a BRCA1 mutation may have molecular characteristics distinct from those of sporadic USC, and further accumulation and analysis of such cases are needed to evaluate the clinical implications.

SATB2 expression can be reliably used in the differential diagnosis of primary endometrial endometrioid and serous carcinomas as well as primary endocervical adenocarcinomas because nearly all of these tumors are SATB2-negative. SATB2 positivity in endometrial carcinomas is almost always restricted to morules within endometrioid adenocarcinomas.

These genetic alterations were conspicuously absent in primary tumors, suggesting their potential role in metastatic progression. Our findings represent the first demonstration of CNV-driven oncogenic evolution in UTROSCTs, particularly implicating SWI/SNF complex dysregulation in metastatic competence.

We established a PDX model of MLA to facilitate personalized treatment for rare tumors.

Among increasingly personalised strategies, particular promise is shown by HER2-targeted therapies for HER2-positive malignancies (e.g. trastuzumab deruxtecan). Additionally, targeting TP53 wild-type tumours with selinexor, as well as addressing AKT and DNA repair pathways in both uterine carcinomas and sarcomas (i.e. AKT inhibitor and poly(ADP-ribose) polymerase inhibitor combinations), represents key advancements. Furthermore, anti-angiogenic and immune checkpoint inhibitor combinations hold significant promise for future therapeutic strategies.

FAM171A2 demonstrates context-dependent expressions that are modulated post-transcriptionally in gynecologic cancers. While it is not independently prognostic, it may serve as a molecular hub at the intersection of neuronal and immune pathways, warranting further mechanistic investigations and exploration as a panel-based biomarker.

Emerging therapeutic approaches aim to restore the tumor-suppressive miRNAs or inhibit oncogenic ones using mimics or antagomiRs. Overall miRNAs represent critical regulators of uLMS pathogenesis and hold significant potential for precision diagnosis, prognostication, and targeted therapy, though larger validation studies and improved delivery systems are required before clinical translation.

P=N/A, N=2500, Recruiting, University Health Network, Toronto | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jul 2026

P=N/A, N=66, Not yet recruiting, Saglik Bilimleri Universitesi Gazi Yasargil Training and Research Hospital