Recurrent Ovarian Cancer with BRCAness Phenotype: A Treatment Challenge

Leão, Inês; Oliveira, Inês; Sousa, Isabel; André, Teresa

doi:10.1007/s12325-022-02259-2

Cited by 7 publications

(3 citation statements)

References 26 publications

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“…With the development of clinical trials, a series of high-level evidence-based medical evidence has shown that maintenance therapy with PARP inhibitors after initial treatment of OC or platinum-sensitive relapsed therapy achieved complete response (CR) or partial response (PR) can signi cantly prolong PFS in patients [50,51]. The exact mechanism is not clear, but it may be related to "capture", that is, PARP inhibitors bind to the niacinamide adenine dinucleotide binding pocket of PARP1/2, forming conformational abnormalities that stabilize DNA-PARP [52][53][54]. Here, we illustrate a new function of PARP1 that is different from the common HR repair function [44,55,56].…”

Section: Discussionmentioning

confidence: 99%

PARP1-stabilized FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway

Guo

et al. 2023

Preprint

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Background: Ovarian cancer (OC) is one of the most common fatal malignancies in females worldwide. Only a few articles have reported that Forkhead box Q1 (FOXQ1) is elevated in OC tissues and associated with prognosis, but its cancer-promoting mechanism has not been clarified. Methods: We analysed the relationship between FOXQ1 expression and clinical prognosis through analyses of public databases and data from our own centre. Subsequently, the carcinogenic effect of FOXQ1 was demonstrated by phenotypic experiments in vitro and in vivo. Mechanistically, downstream transcriptional regulatory molecules and signalling pathways were identified by RNA-seq, ChIP-seq, KEGG and GSEA, and promoter binding sites were identified by luciferase reporter gene assay. The upstream regulatory relationship is explored through Co-IP, immunofluorescence (IF), mass spectrum (MS) and ubiquitination experiments. Finally, this pathway was verified by small animal drug experiments and the relationship between clinical specimens and prognosis. Results: Here, we show that FOXQ1 is overexpressed in OC and clinically associated with metastasis and patient prognosis. FOXQ1 significantly promotes OC cell proliferation and metastasis in vitro and in vivo. Mechanistically, FOXQ1 can promote LAMB3 transcription by binding to its promoter region. The oncogenic effects of FOXQ1 are mediated by theLAMB3/WNT/β-catenin pathway. Moreover, PARP1 can inhibit the ubiquitination-mediateddegradation of FOXQ1 by targeting the E3 ubiquitin ligase CHIP. Finally, the role of PARP1/FOXQ1/LAMB3/WNT/β-catenin pathway in OC was demonstrated through drug combination experiments in animals and clinical prognosis. Conclusions: Taken together, our data indicate that FOXQ1, stabilized by PARP1, can promote the progression of OC through the LAMB3/WNT/β-catenin pathway.

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Section: Discussionmentioning

confidence: 99%

PARP1-stabilized FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway

Guo

et al. 2023

Preprint

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“…Ovarian cancer is one of the most common cancers and a leading cause of mortality among women [1]. It is often diagnosed at an advanced stage, resulting in poor health outcomes.…”

Section: Introductionmentioning

confidence: 99%

Beta-HCG levels and ovarian ultrasonography results among non-pregnant women of reproductive age in Port Harcourt, Nigeria

Agonsi,

Anacletus,

Aluko

et al. 2023

Preprint

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Background Certain ovarian cancers previously more common in postmenopausal women are now increasingly observed in women of reproductive age. The research on using β-HCG as a diagnostic biomarker for ovarian cancer in women of reproductive age is ongoing. This particular study assessed the level of serum β-HCG in non-pregnant women of reproductive age and determined its potential association with suspicious ovarian ultrasonography results in Port Harcourt, Nigeria. Material and methods This study utilized a descriptive-analytic design on a quota sample of 224 diagnostic case notes of women aged 18-40. Data collection involved a data extraction form. Data analysis employed descriptive statistics, Chi-square, Fisher's exact test, and Odds Ratio at 95% confidence and 5% significance levels. Results About 5.8% of the participants exhibited detectable levels of serum β-HCG above 5 IU/L (World Health Organization reference) at a mean concentration of 5.87 (±1.75) IU/L. About 4% of the participants had suspicious ovarian lesions identified through ultrasonography. Participants with elevated serum β-HCG levels above the WHO reference were 59 times more likely to have suspicious ovarian lesions, with an odds ratio of 59.4 (95%CI: 12.3–287.8, p = 0.001). There was a significant association between serum β-HCG level and age (p = 0.041) as well as parity (p < 0.001). Conclusions This study demonstrated that Serum β-HCG levels above the WHO reference were associated with suspicious ovarian lesions. Non-pregnant women should undergo serum β-HCG testing at least yearly to facilitate the early detection of ovarian anomalies.

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“…All qualities (tumor stage, tumor subtype and quantitatively measuring tumor heterogeneity) are essential principles that guide the treatment decision-making process and shape the direction of clinical research [ 33 ]. Moreover, molecular and genetic features, including germline and somatic breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) mutations [ 34 , 35 ], may influence the prognosis of patients [ 36 , 37 ], the recurrence rate [ 38 ], and the cancer response to DNA-damaging agents, such as platinum chemotherapy [ 39 ], or DNA repair pathways inhibitors. Poly-ADP-ribose polymerase inhibitors (PARPi) have recently shown to be effective as a first-line or maintenance treatment for patients with advanced BRCA-mutated ovarian cancer [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes

Marrelli

Ansaloni²,

Federici

et al. 2022

Cancers

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Ovarian cancer is the eighth most common neoplasm in women with a high mortality rate mainly due to a marked propensity for peritoneal spread directly at diagnosis, as well as tumor recurrence after radical surgical treatment. Treatments for peritoneal metastases have to be designed from a patient’s perspective and focus on meaningful measures of benefit. Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery with regional chemotherapy, has been proposed to treat advanced ovarian cancer. Preliminary results to date have shown promising results, with improved survival outcomes and tumor regression. As knowledge about the disease process increases, practice guidelines will continue to evolve. In this review, we have reported a broad overview of advanced ovarian cancer management, and an update of the current evidence. The future perspectives of the Italian Society of Surgical Oncology (SICO) are discussed conclusively.

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Recurrent Ovarian Cancer with BRCAness Phenotype: A Treatment Challenge

Cited by 7 publications

References 26 publications

PARP1-stabilized FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway

PARP1-stabilized FOXQ1 promotes ovarian cancer progression by activating the LAMB3/WNT/β-catenin signalling pathway

Beta-HCG levels and ovarian ultrasonography results among non-pregnant women of reproductive age in Port Harcourt, Nigeria

Cytoreductive Surgery (CRS) and HIPEC for Advanced Ovarian Cancer with Peritoneal Metastases: Italian PSM Oncoteam Evidence and Study Purposes

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