Pilot Feasibility and Efficacy Trial of a Novel Reversible LSD1 Inhibitor SP-2577 (Seclidemstat) Plus Pembrolizumab in Select SWI/SNF-mutant Gynecologic Cancers

Open-label study of SF-2577 plus pembrolizumab in advanced, recurrent small cell ovarian cancer as well as select additional ovarian and endometrial cancers within the SWI/SNF pathway.

Start Date31 Dec 2021

Sponsor / Collaborator

HonorHealth Ambulatory

[+2]

NCT05226507

/ RecruitingPhase 1

A Phase 1 Clinical Study of NXP800 in Subjects with Advanced Cancers and Expansion in Subjects with Ovarian Cancer

The purpose of the dose escalation phase is to evaluate the safety profile of escalating doses and dose schedules of NXP800. In the expansion phase the preliminary efficacy in subjects with ARID1a mutated ovarian clear cell and ovarian endometrioid cancers will be estimated.

Start Date31 Dec 2021

Sponsor / Collaborator

Nuvectis Pharma, Inc.

[+2]

CTR20201170

/ TerminatedPhase 1/2

一项MAK683用于晚期恶性肿瘤成人患者的I/II期、多中心、开放性研究

[Translation] A Phase I/II, Multicenter, Open-label Study of MAK683 in Adult Patients with Advanced Malignancies

本项I/II期研究目的在晚期恶性肿瘤患者中（非霍奇金淋巴瘤、鼻咽癌或目前无更多有效标准治疗方法的其他晚期实体瘤）确定MAK683的最大耐受剂量（MTD）和/或II期推荐剂量（RP2D）并评估安全性、抗肿瘤活性和药代动力学（PK）特征

[Translation]

The purpose of this Phase I/II study is to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of MAK683 in patients with advanced malignancies (non-Hodgkin's lymphoma, nasopharyngeal carcinoma, or other advanced solid tumors for which no more effective standard treatments are currently available) and to evaluate safety, antitumor activity, and pharmacokinetic (PK) characteristics.

Start Date30 Sep 2021

Sponsor / Collaborator

China Novartis Institutes for BioMedical Research Co., Ltd.

[+1]

100 Clinical Results associated with Clear cell neoplasm of ovary

100 Translational Medicine associated with Clear cell neoplasm of ovary

0 Patents (Medical) associated with Clear cell neoplasm of ovary

Literatures (Medical) associated with Clear cell neoplasm of ovary

01 Apr 2025·Anti-Cancer Drugs

FSP1 expression as a predictor of platinum resistance and recurrence in epithelial ovarian cancer

Article

Author: Yin, Qi ; Bi, Hai-Ning ; Gong, Xue-Mei ; Xing, Hang ; Li, Yao-Jiao ; Shi, Ji-Fang ; Zhang, Xue ; Zhang, Ji

The objective of this study is to assess the differential expression of ferroptosis suppressor protein 1 (FSP1) in relation to clinical features, platinum resistance, and recurrence in epithelial ovarian cancer (EOC). In addition, the potential significance of FSP1 in EOC as a predictor of platinum resistance and recurrence in EOC was explored. Patients with pathologically confirmed EOC who underwent surgical treatment were included in this analysis. Immunohistochemistry was employed to evaluate FSP1 expression in ovarian tissues, with quantitative analysis performed on the samples. Clinical data were collected during follow-up, and patients were categorized according to platinum resistance and recurrence criteria. Statistical analysis was conducted using SPSS version 27.0. A total of 40 tissue samples from patients with EOC were analyzed, along with 21 samples from benign ovarian tumors and 20 samples from normal ovarian tissues. The expression of FSP1 was significantly higher in the EOC group compared to both benign and normal tissue groups. Meanwhile, the expressions of FSP1 were higher in groups with clinically advanced stages, high-grade carcinoma, presence of cancerous ascites, lymph node metastasis, and in the clear cell EOC group, compared to those with clinically early stages, low-grade carcinoma, absence of cancerous ascites, no lymph node metastasis, and other pathological subtypes. A positive linear correlation was identified between FSP1 expression in EOC tissues and serum levels of CA125 and human epididymis protein 4 at the time of diagnosis. The elevated expression of FSP1 is positively correlated with serum CA125 and human epididymis protein 4 levels at the time of diagnosis, which is a risk factor for EOC drug resistance and recurrence. These findings suggest that FSP1 may serve as a valuable biomarker for predicting platinum resistance and recurrence in patients with EOC.

01 Jun 2024·eBioMedicine

Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study

Article

Author: Tworoger, Shelley S ; Richmond, Rebecca C ; Redline, Susan ; Lane, Jacqueline M ; Wang, Heming ; Reid, Brett M ; Saxena, Richa ; Wang, Xuefeng ; Gonzalez, Brian D ; Fridley, Brooke L

BACKGROUNDInsomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study.METHODSInsomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors.FINDINGSInsomnia was associated with higher risk of endometrioid EOC (OR = 1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR = 0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR = 1.45, 95% CI 1.13-1.87) and HGSOC (OR = 1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR = 2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors.INTERPRETATIONThis study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival.FUNDINGNational Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.

01 May 2024·The Journal of Steroid Biochemistry and Molecular Biology

The effect of androgens on the risk of endometriosis sub-phenotypes and ovarian neoplasms: A Mendelian randomization study

Article

Author: Rizner, Tea Lanisnik ; Gjorgoska, Marija

Endometriosis is a complex gynecological pathology with a broad spectrum of symptoms, affecting around 10% of reproductive-aged women. Ovarian cancer (OC) is a heterogeneous disease for which we lack effective diagnostic and therapeutic strategies. The etiology and pathogenesis of both diseases remain ambiguous. Androgens in endometriosis could have a distinct role beyond serving as estrogen sources, whereas in the case of serous OC could be important in the formation of precursor lesions which ultimately lead to tumor formation. Here we performed two-sample Mendelian randomization (MR) analysis to examine the causal relationship between the androgen precursor - dehydroepiandrosterone sulphate (DHEAS), bioactive androgen - testosterone (T), androgen metabolite - androsterone sulphate, steroid hormone binding globulin (SHBG) and albumin and the risk of endometrioses of various sub-phenotypes and ovarian neoplasms across the benign-borderline-malignant spectrum. Stringent quality control procedures were followed to select eligible instrumental variables that were strongly associated with the selected exposures, sensitivity analyses were performed to assess the heterogeneities, horizontal pleiotropy, and stabilities of SNPs in endometriosis and ovarian neoplasms. We discovered an inverse association between genetically predicted levels of all androgens and risk of endometriosis, the same trend was most evident in the ovarian sub-phenotype. Total T levels were also inversely associated with peritoneal sub-phenotype of endometriosis. Likewise, T was causally associated with decreased risk of clear-cell OC, an endometriosis-associated OC subtype, and with malignant serous OC of both low- and high-grade, but with higher risk of their counterpart of low malignant potential. These findings support further investigation of androgen's action at a molecular level in ovary-associated endometriotic lesions, clear cell ovarian tumors and serous precursor lesions.

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