Uterine Cancer

P1, N=42, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027

Comprehensive genomic profiling of advanced-stage TOC and UC via WGS reveals key biomarkers and therapeutic targets, enhancing diagnostic accuracy and advancing personalized medicine in gynecological cancers.

Furthermore, the presence of m7G RNA methylation in UCEC cells also was found. In conclusion, the methylation of EXT1 influenced the gene expression, thereby affecting the malignant biological behaviors in UCEC cells and regulating the pathological progression of UCEC.

Patients with higher PPP1R14B expression responded more sensitively to drugs selumetinib and vorinostat, zebularine, azacitidine and VER155008. In summary, PPP1R14B was a potential diagnostic and prognostic biomarker of PCa and its high expression had closely association with tumor immune inhibition, proliferation and migration, providing a new target for drug therapy and immunotherapy in PCa.

No abstract available

miR-1301-3p regulates the proliferation and migration of UCEC cells by interacting with the FHL1 gene. miR-1301-3p may serve as a promising prognostic biomarker in UCEC.

P2, N=60, Not yet recruiting, MacroGenics

Clinical specimen characteristics also confirmed a negative correlation between IL-33 expression and UCEC staging and grading. This comprehensive analysis of IL-33, based on bioinformatics and immunohistochemistry, revealed that IL-33 has the function of inhibiting UCEC occurrence and progression and can be served as a beneficial prognostic marker in the clinic.

The final diagnosis was leiomyoma coexisting with low-grade ESS, classified as International Federation of Gynecology and Obstetrics (FIGO) stage IB. The patient received no further treatment and remains disease-free after 45 months.

Compared with those in Ishikawa-Vector, the levels of GSH significantly decreased and those of MDA significantly increased in Ishikawa-FANCD2KD treated with different concentrations of cisplatin. FANCD2 was highly expressed in UCEC, and the down-regulation of FANCD2 affected the levels of GSH and MDA to increase the cisplatin sensitivity of Ishikawa cells.

The prognostic model comprising ARPC1B, BATF, CCL2, and COTL1 can effectively identify high-risk EC patients and predict their response to immunotherapy, demonstrating significant clinical potential. These genes are implicated in EC development and immune infiltration, with BATF emerging as a potential therapeutic target for EC.

The identified miRNAs and TFs have significant roles in regulating these genes, providing valuable insights into the molecular pathways that underlie UC. These findings offer promising opportunities to develop innovative diagnostic and therapeutic approaches for UC.

No abstract available

Regarding responses, 5 patients had partial response (including 2 patients that were pretreated with trastuzumab), 1 patient had stable disease at 12 weeks and 4 patients had disease progression at initial assessment. All patients but one that derived clinical benefit had HER2 3 + expression.DiscussionIn the real-world setting, T-DXd showed activity in a cohort of heavily pre-treated patients with HER2-expressing gynecological malignancies.

These data indicate that highly selective ERβ agonism can facilitate object recognition memory in both APOE3 homozygotes and APOE3/4 heterozygotes, but only reduce the magnitude of a drug-induced hot flash in APOE3 homozygotes, suggesting that APOE4 genotype may blunt the beneficial effects of ET on hot flashes. Collectively, these data suggest a potentially beneficial effect of selective ERβ agonism for memory and hot flashes in females with AD-like pathology, but that APOE genotype plays an important role in responsiveness.

Of the 8 patients with available follow-up, two died of disease, 3 are currently alive with disease, and 3 have no evidence of disease. The correct recognition of tumors with the KAT6B/A::KANSL1 fusion is essential because despite the bland morphological features of most cases, these tumors have a propensity for aggressive behavior.

PRAME over-expression in gynecological tumors supports the notion that this marker should not be regarded as specific to MM alone. EC exhibited higher PRAME expression than CC and OC, and low-grade EEC displayed higher PRAME immunoreactivity than other EC types. Our findings suggest that PRAME immunostaining can be useful to distinguish EEC from ovarian endometrioid carcinoma and endocervical adenocarcinoma. PRAME over-expression can also help differentiate non-aggressive EC from aggressive EC.

Our study supports full molecular classification of UCS. We also raise awareness for potentially assessing POLE mutation allele fraction and clonality in the consideration of classifying a tumor as POLEmut.

In vivo studies in mouse xenograft demonstrated that it promoted uterine cancer tumorigenesis. In this chapter, we delineate the methodologies we used in studying PLK1 O-GlcNAcylation, including click chemistry, stepped collisional energy/higher energy collision dissociation mass spectrometry, fluorescent activated cell sorting, time-lapse microscopy, and mouse xenograft assays.

P1/2, N=37, Recruiting, University of Alabama at Birmingham | Trial primary completion date: Dec 2024 --> Apr 2025

Ferroptosis analysis indicated that ALOX5 and VLDLR were the top CAPG-related ferroptosis markers; glutathione metabolism levels in tumor group were generally high, and decitabine was a ferroptosis inducer...Moreover, four chemotherapy drugs showed better sensitivity to UCEC patients in the low-risk cohort. CAPG may serve as a potential biomarker of UCEC owing to its role in modulating the immune response and ferroptosis, providing novel perspectives for combined immunotherapy of UCEC.

Of the six cases of endometrial adenocarcinoma with follow-up available, four received a post-surgical treatment with meloxicam and two were treated by surgery alone...Our findings suggest the possible use of COX-2 inhibitors in treating uterine adenocarcinoma in rabbits. Further study will be needed to confirm this hypothesis.

Clinical and histological features resemble high-grade endometrial carcinoma, necessitating an extensive IHC panel to narrow down differentials and confirm the diagnosis. This study highlights the histological and IHC features and emphasizes that early diagnosis plays a crucial role in disease management.

P=N/A, N=247, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=80 --> 247

To our knowledge, we report the first case of a soft tissue tumor with a PLAG1 fusion gene in an adult. In our case, we detected a new H3-3B::PLAG1 fusion in a soft tissue tumor, which originally appeared as nodular fasciitis.

P2, N=76, Recruiting, K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc | Active, not recruiting --> Recruiting

This analysis study identified the hub genes and associated pathways involved in the pathogenesis of UCEC. The identified hub genes exhibit remarkable potential as diagnostic biomarkers, providing a significant opportunity for early diagnosis and more effective therapeutic approaches for UCEC.

Our research provides insights into the significance of FOXK2 in cancer and indicates its potential as both a prognostic indicator and target for treatment. The ribosome-associated pathways involving FOXK2 and FBXO32 could be pivotal in the advancement of tumors, offering possible avenues for targeted and individualized immunotherapy approaches. Additional research is required to completely understand the mechanisms that are responsible for the participation of FOXK2 and its subsequent gene FBXO32 in cancer, as well as to explore the possible advantages of focusing on FOXK2 for cancer treatment.

Based on these findings, the patient was diagnosed with stage IIIC2 endometrial cancer (pT1bN2M0, clear cell carcinoma) and received postoperative adjuvant therapy with paclitaxel and carboplatin. Five cycles of pembrolizumab and lenvatinib followed by four cycles of doxorubicin and cisplatin were ineffective. The patient died 13 months after the diagnosis of recurrence.

P1, N=26, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Nov 2024 | Trial primary completion date: Apr 2025 --> Nov 2024

Mechanistically, PP2A regulated IGFBP2 expression through the transcription factor, NF-κB, which harbors a B56 recognition motif. Collectively, these results identify a role for PP2A in regulating paracrine cancer cell signaling that can be targeted to block the initiation and metastasis of high-grade uterine cancer.

P1, N=50, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

ET/HT can probably be used after ovarian neoplasms except for granulosa cell tumors, and with great caution after low-grade serous ovarian carcinoma and serous borderline ovarian tumors. ET/HT can be used with great caution in women after estrogen receptor (ER)/progesterone receptor (PR)-positive breast cancer and is probably allowed after ER/PR-negative breast cancer.

P=N/A, N=23, Active, not recruiting, City of Hope Medical Center | Recruiting --> Active, not recruiting | N=75 --> 23

P=N/A, N=1000, Recruiting, M.D. Anderson Cancer Center | N=50 --> 1000 | Trial completion date: Jun 2024 --> Jun 2028 | Trial primary completion date: Jun 2024 --> Jun 2028

Key stakeholders came together including basic scientists, clinical investigators, and patient advocates to identify critical research gaps that, when addressed, would facilitate more comprehensive and rapid progress in understanding and ultimately treating USC across all patients. NCI released a supplemental funding opportunity (NOT-CA-24-044) in Spring 2024 to facilitate rapid translation of these recommendations.

Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.

P2, N=85, Active, not recruiting, Huazhong University of Science and Technology | Recruiting --> Active, not recruiting

P=N/A, N=25, Recruiting, University of Virginia | Not yet recruiting --> Recruiting

P1/2, N=54, Recruiting, Icahn School of Medicine at Mount Sinai | Not yet recruiting --> Recruiting

This case demonstrates one of the few reports of a giant cystic adenomatoid tumor (11.5 cm) and highlights diagnostic mimics. As these tumors are typically small and often seen only microscopically, the large size can confuse the pathologist who may be unaware of this feature leading to a misdiagnosis.

P3, N=774, Completed, Huazhong University of Science and Technology | Unknown status --> Completed