更新于：2024-11-01

endometrial clear cell carcinoma

子宫内膜透明细胞癌

更新于：2024-11-01

基本信息

别名

Clear Cell Carcinoma of Endometrium、Clear Cell Carcinoma of the Endometrium、Clear cell endometrial carcinoma

+ [10]

简介

A high-grade endometrial adenocarcinoma characterized by the presence of large neoplastic cells that display at least focal cytoplasmic clearing. The neoplastic cells form papillary, glandular, or sheet-like structures.

关联

项与子宫内膜透明细胞癌相关的药物

Mirvetuximab soravtansine

索米妥昔单抗

靶点

FOLR1 x Tubulin

作用机制

FOLR1拮抗剂 [+1]

在研机构

BSP Pharmaceuticals SpA [+5]

原研机构

ImmunoGen, Inc.

在研适应症

铂耐药上皮性卵巢癌 [+18]

非在研适应症

子宫内膜透明细胞癌 [+1]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2022-11-14

Selumetinib sulfate

司美替尼

靶点

MEK1 x MEK2

作用机制

MEK1抑制剂 [+1]

在研机构

National Cancer Institute [+11]

原研机构

Array BioPharma, Inc.

在研适应症

神经纤维瘤病 [+53]

非在研适应症

急性早幼粒细胞白血病 [+65]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2020-04-10

Nintedanib esylate

乙磺酸尼达尼布

靶点

CSF-1R x FGFRs x FLT3 x PDGFR x VEGFR

作用机制

CSF-1R拮抗剂 [+4]

在研机构

Boehringer Ingelheim International GmbH [+11]

原研机构

Boehringer Ingelheim International GmbH

在研适应症

间质性肺疾病 [+17]

非在研适应症

大肠腺癌 [+48]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2014-10-15

项与子宫内膜透明细胞癌相关的临床试验

NCT06638931 / Recruiting临床2期IIT

Phase II Basket Study to Evaluate the Tissue-agnostic Efficacy of Anti-Programmed Cell Death Protein 1 (Anti-PD1) Monoclonal Antibody in Patients With Advanced Rare Tumors

The ANTARES study is a phase II basket trial designed to evaluate the tissue-agnostic efficacy of the monoclonal anti-PD1 antibody, nivolumab, in patients with advanced or metastatic rare tumors.
The study aims to treat rare malignancies with PD-L1 expression (CPS ≥ 10), regardless of the tumor's tissue type or location. Patients who have not responded to standard treatments will be included, and treatment will last for up to 12 months. The study will assess objective response, progression-free survival, and biomarkers such as PD-L1, ctDNA, and microvesicles, in a multicenter collaborative effort to provide innovative therapeutic options for this underrepresented population

开始日期2024-07-01

申办/合作机构

Instituto do Cancer do Estado de Sao Paulo

[+1]

NCT05950464 / Recruiting临床1期IIT

A Phase 1B Study of Combination ATR (M1774) and BET Inhibition (ZEN00-3694) to Exploit ARID1A Loss in Recurrent Ovarian and Endometrial Cancer

This phase Ib trial tests the safety, side effects, and best dose of M1774 when given with ZEN-3694 in treating patients with ovarian and endometrial cancer that has come back (recurrent). M1774 and ZEN-3694 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. M1774 and ZEN-3694 combined together has demonstrated to be better than either drug alone in killing ovarian tumor cells.

开始日期2023-12-18

申办/合作机构

National Cancer Institute

[+1]

NCT05498597 / Recruiting临床1期

First-in-Human, Phase 1 Study of AMT-151, an Anti-Folate Receptor Alpha Antibody-Drug Conjugate, in Patients With Selected Advanced Solid Tumours

This first-in-human study will evaluate the Maximum Tolerated Dose (MTD) / the Recommended Phase 2 Dose (RP2D), safety, tolerability, anti-tumor activity, pharmacokinetics, pharmacodynamics and immunogenicity of AMT-151, a novel antibody-drug conjugate against folate receptor alpha, in patients with selected advanced solid tumors.

开始日期2023-01-25

申办/合作机构

Multitude, Inc.

[+1]

100 项与子宫内膜透明细胞癌相关的临床结果

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100 项与子宫内膜透明细胞癌相关的转化医学

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0 项与子宫内膜透明细胞癌相关的专利（医药）

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730

项与子宫内膜透明细胞癌相关的文献（医药）

2024-11-01·Gynecologic Oncology

Impact of adjuvant therapy on oncologic outcomes in uterine-confined clear cell carcinoma of the endometrium

Article

作者: Leitao, Mario M ; Abu-Rustum, Nadeem R ; Eriksson, Ane Gerda ; Sassine, Dib ; Mueller, Jennifer J ; Abu-Rustum, Nadeem R. ; Makker, Vicky ; Nobre, Silvana Pedra ; Rios-Doria, Eric ; Mueller, Jennifer J. ; Glaser, Gretchen ; Alektiar, Kaled ; Ataseven, Beyhan ; Leitao, Mario M. ; du Bois, Andreas

OBJECTIVESTo determine the impact of adjuvant therapy on oncologic outcomes in patients with 2009 International Federation of Gynecology and Obstetrics (FIGO) stage IA, IB, or II endometrial clear cell carcinoma (ECCC).METHODSWe conducted a retrospective review at 4 international institutions. Patients with newly diagnosed clinical stage I or II disease of either clear cell or mixed histology with a clear cell component treated between 01/01/2000-12/31/2015 were included. Oncologic outcomes were assessed for patients based on adjuvant treatment received, including chemotherapy, radiation, or chemotherapy with radiation.RESULTSOf 125 patients identified and analyzed, 77 (61.6%) had clear cell histology and 118 (94.4%) had stage I disease. Median age at diagnosis was 65 years (range, 33-91). All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. Twenty-five patients (20.0%) underwent surgical management alone and 100 (80.0%) received adjuvant therapy: 20 (16.0%) received postoperative chemotherapy, 47 (37.6%) received postoperative radiation, and 33 (26.4%) received postoperative chemotherapy with radiation. Median follow-up was 88.4 months (range, <1-234). Progression-free survival (PFS) or overall survival (OS) did not significantly differ between surgery alone and type of adjuvant therapy (P = 0.18 and P = 0.56, respectively). Patients with mixed ECCC did not have a survival advantage over those with pure ECCC (5-year PFS rate, 85.0% vs 82.7%, P = 0.77; 5-year OS rate, 88.3% vs 91.2%, P = 0.94).CONCLUSIONSReceipt of adjuvant therapy in surgically staged I/II ECCC did not appear to offer a survival advantage over observation alone. Adjuvant therapy in early-stage ECCC with consideration of molecular classification should be evaluated.

2024-10-01·Journal of Biological Chemistry

14-3-3ε augments OGT stability by binding with S20-phosphorylated OGT

Article

作者: Yao, Xinyi ; Li, Jing ; Yan, Sheng ; Sun, Jianwei ; Yuan, Kemeng ; Chen, Qiang

The relationship between O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and mitosis is intertwined. Besides the numerous mitotic OGT substrates that have been identified, OGT itself is also a target of the mitotic machinery. Previously, our investigations have shown that Checkpoint kinase 1 (Chk1) phosphorylates OGT at Ser-20 to increase OGT levels during cytokinesis, suggesting that OGT levels oscillate as mitosis progresses. Herein we studied its underlying mechanism. We set out from an R17C mutation of OGT, which is a uterine carcinoma mutation in The Cancer Genome Atlas. We found that R17C abolishes the S20 phosphorylation of OGT, as it lies in the Chk1 phosphorylating consensus motif. Consistent with our previous report that pSer-20 is essential for OGT level increases during cytokinesis, we further demonstrate that the R17C mutation renders OGT less stable, decreases vimentin phosphorylation levels and results in cytokinesis defects. Based on bioinformatic predictions, pSer-20 renders OGT more likely to interact with 14-3-3 proteins, the phospho-binding signal adaptor/scaffold protein family. By screening the seven isoforms of 14-3-3 family, we show that 14-3-3ε specifically associates with Ser-20-phosphorylated OGT. Moreover, we studied the R17C and S20A mutations in xenograft models and demonstrated that they both inhibit uterine carcinoma compared to wild-type OGT, probably due to less cellular reproduction. Our work is a sequel of our previous report on pS20 of OGT and is in line with the notion that OGT is intricately regulated by the mitotic network.

2024-09-01·Gynecologic Oncology

The prognostic impact of substantial lymphovascular space invasion in women with node negative FIGO stage I uterine carcinoma

Article

作者: Allo, Ghassan ; Elshaikh, Mohamed A ; Lin, Chun-Hui ; Ghanem, Ahmed I ; Bhatnagar, Aseem Rai ; Alkamachi, Bassam ; Hijaz, Miriana

OBJECTIVESubstantial lymphovascular space invasion (LVSI) is an important predictor of lymph node (LN) involvement in women with endometrial carcinoma. We studied the prognostic significance of substantial LVSI in patients with 2009-FIGO stage-I uterine endometrioid adenocarcinoma (EC) who all had pathologic negative nodal evaluation (PNNE).METHODSPathologic specimens were retrieved and LVSI was quantified (focal or substantial) in women with stage-I EC who had a hysterectomy and PNNE. In addition to multivariate analysis (MVA), recurrence-free (RFS), disease-specific (DSS), and overall (OS) survival was compared between women with focal vs. substantial LVSI.RESULTS1052 patients were identified with a median follow-up of 9.7 years. 358 women (34%) received adjuvant radiotherapy. 907 patients (86.2%) had no LVSI, 87 (8.3%) had focal, and 58 (5.5%) had substantial LVSI. Five-year RFS was 93.3% (95% CI: 91.5-95.1), 76.8% (95% CI: 67.2-87.7) and 79.1% (95% CI: 67.6-95.3) for no, focal, and substantial LVSI(p < 0.0001). There was no statistically significant difference in 5-year RFS, DSS, OS, and in the patterns of initial recurrence between women with focal vs substantial LVSI. On MVA with propensity score matching, substantial LVSI was not independently associated with any survival endpoint compared to focal LVSI, albeit both were detrimental when compared to no LVSI. Age ≥ 60 years and higher grade were predictors of worse RFS, DSS, and OS. Additionally, comorbidity burden was an independent predictor for OS.CONCLUSIONSOur results suggest that substantial LVSI does not predict worse survival endpoints or different recurrence patterns in women with stage-I EC with PNNE when compared to focal LVSI.