Ovarian Serous Adenocarcinoma

In addition, LIN28B could regulate the expression of the downstream factor ubiquitin D (UBD) in SOC cells, further promoting the development of SOC. This study shows that ZNF384 aggravates the malignant behavior of SOC cells through the LIN28B/UBD axis, which may be used as a diagnostic biomarker for patients with SOC.

Our results suggest a causal relationship between cathepsins and ovarian malignancy and its subtypes. Cathepsin L2 has a protective effect on low-grade serous ovarian cancer, whereas cathepsin H is an adverse risk factor for clear cell ovarian cancer.

P2, N=40, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed

Importantly, co-targeting N-cadherin and p110α/AKT caused additive reduction in cell migration in vitro and metastases formation in vivo. Together, this study reveals the molecular pathways driven by the PIK3CA aberrations and the exploitable vulnerabilities in PIK3CA-aberrated serous ovarian cancer cells.

Positive β-catenin expression significantly correlated with tumor grade in serous ovarian carcinoma. Most low-grade serous carcinoma cases exhibited membranous β-catenin expression, whereas high-grade serous carcinoma cases predominantly displayed cytoplasmic staining. Therapeutic strategies aimed at inhibiting β-catenin signaling could provide a novel approach to improving outcomes for patients with high-grade ovarian cancer.

P2, N=33, Recruiting, North Eastern German Society of Gynaecological Oncology | Trial primary completion date: Nov 2024 --> Apr 2025

The TruSight Oncology 500 comprehensive solid tumor next-generation sequencing panel with HRD assay demonstrated a high degree of sensitivity and specificity for deployment in a clinical setting.

P2, N=15, Recruiting, Verastem, Inc.

P2, N=130, Active, not recruiting, Dana-Farber Cancer Institute | Recruiting --> Active, not recruiting | Trial completion date: Aug 2029 --> Aug 2030 | Trial primary completion date: Aug 2026 --> Aug 2027

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.

P1, N=34, Recruiting, University of Utah | Trial primary completion date: Aug 2024 --> Apr 2024

There is no definitive therapeutic algorithm for advanced ovarian cancer, despite ongoing efforts and multiple proposed tools. Future research should focus on expanding the utility of biomarkers, reducing resistance, and increasing the actionable biomarker pool.

We also assume that the immune system may play a pivotal role in the transition from BOTS to lgOvCa. Given that the BOT.V600E tumors had the lowest number of DM CpGs and DMRs compared to all other groups, when methylome is considered, such tumors might be placed in-between BOT and OvCa.

The patient received neoadjuvant chemotherapy with a combination of carboplatin and gemcitabine followed by optimal debulking surgery and was alive after 18 months of follow up. The management of this rare case remains unclear due to the absence of management guidelines.

Database analysis showed that high-level expression of YKL40 and integrin β4 correlated with a poor prognosis in patients with serous ovarian carcinoma. Therefore, the YKL40/integrin β4 axis may play a role in ovarian cancer progression.

P2, N=61, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

This is translated into a reduced FAK activity at FAs, ECM-dependent alterations of mechanical forces through FAs and YAP nuclear translocation. Together, the data show that low expression, silencing or inhibition of VEGFR2 in HGSOC cells alter mechanotransduction and lead to the acquisition of a pro-proliferative/invasive phenotype which explains the need for a more cautious use of anti-VEGFR2 drugs in ovarian cancer.

Activation of the same signaling pathway occurs in HGSOC PDXs that are resistant to poly(ADP-ribose) polymerase inhibitors but respond to RCMs ex vivo with a decrease in cell number in 3-dimensional culture and in vivo with xenograft shrinkage or a significantly diminished growth rate. These findings identify key cell death-initiating events that link replication checkpoint inhibition to antitumor response in ovarian cancer.

The estimated primary completion date of RAMP 301 is 2028, and the estimated study completion date is 2031. ClinicalTrials.gov NCT06072781.

In contrast, pre-ciliated cells (Krt5+, Prom1+, Trp73+) remain cancer-prone and give rise to serous tubal intraepithelial carcinomas and overt HGSC. These findings identify transitional pre-ciliated cells as a cancer-prone cell state and point to pre-ciliation mechanisms as diagnostic and therapeutic targets.

Though less than in high-grade disease, a notable portion of low-grade tumors were FOLR1+, suggesting FOLR1 expression in LGSOC could be a viable target for this rare histology, particularly in the recurrent setting.

116 patients with a confirmatory primary diagnosis of TNBC (N= 75) and HGSOC (N= 41) were included. A higher Native American ancestry (NAM) proportion was observed in the hereditary group across the cohort (58% vs 45.2%). Among TNBC patients, hereditary cases exhibited a higher NAM ancestry mean (0.50 (SD, 0.14)).

80% of patients had detectable ctDNA at baseline (mutant DNA copies/ml) with somatic mutations found in TP53, BRCA1, KRAS, NRAS, MET and ERBB2 genes. CNVs were found in EGFR and MET. 69% of all plasmas were ctDNA+.

Misfolded p53 protein, prone to aggregation, is present in STICs and HG-SOCs, but notably absent from preneoplastic lesions and surrounding healthy tissue. Overall, our results indicate that aggregation of mutant p53 is a structural defect that distinguishes preneoplastic early lesions from late premalignant and malignant ones, offering a potential treatment window for targeting p53 aggregation and halting ovarian cancer progression.

Enhanced mast cell numbers, as well as activation and degranulation are a consequence of NACT exposure. Post-NACT mast cells displayed differing associations with survival outcomes that was dependent upon granule classification. Ultimately, mast cells represent a clinically relevant putative HGSOC immune target.

Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome.

Plasma CP levels decreased significantly after NACT, and higher CP levels after NACT were associated with a shorter platinum-free interval (PFI). These findings suggest that the ATP7A transporter and CP have the potential to serve as predictive markers of chemoresistance, but further research is needed to validate their clinical utility.

This finding suggests that the PIK3CA gene should be considered in Cowden-like families when no other gene mutations have been found. Furthermore, this report contributes to characterization of the clinical phenotype caused by mutations in PIK3CA, which may be shared with other hereditary breast and ovarian cancer syndromes.

After surgery, TC (Paclitaxel + Carbopratin) + bevacizumab therapy was administered as adjuvant chemotherapy followed by bevacizumab as maintenance therapy. DNA methylation analysis did not show differentially methylated regions. This case suggests that SBT and LGSC may transform into HGSC via p53 dysfunction due to MDM2 amplification.

Furthermore, we demonstrate that detecting distinct colocalized biomarkers on the surface of EVs significantly improves discrimination performance relative to single biomarker measurements. Using this approach, we observe promising discrimination of high-grade serous ovarian cancer versus benign ovarian masses and healthy women in a proof-of-concept clinical study.

Our data also demonstrated that chemotherapy inhibited interferon-dependent signaling pathways, but activated some TGFb-related genes. Our results can enable personalized decision regarding the necessity to systemically re-educate immune cells to prime ovarian cancer to respond to anti-cancer therapy or to improve personalized prescription of existing immunotherapy in either combination with chemotherapy or a monotherapy regimen.

The efficacy of maintenance treatment with PARPi is independent by BRCA domain defects or mutation types. Patients DBD domain defects experienced numerically longer median PFS compared to those with other BRCA1/2 alterations.

P3, N=579, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2025

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: To evaluate the predictive value of the prognostic factor HRD status, as determined by various clinically validated HRD assays at the time of staging laparotomy, compared to BRCA1/2 mutation status for progression-free survival and overall survival in patients with tubo-ovarian high-grade serous carcinoma treated in the first-line setting with a combination of surgery and platinum-based chemotherapy and/or maintenance with PARP inhibitors.

P=N/A, N=3000, Enrolling by invitation, Abramson Cancer Center at Penn Medicine | N=450 --> 3000

Remarkably, this enhanced cytotoxicity is reversed by ferrostatin-1 and the iron chelator deferoxamine, highlighting the pivotal roles of lipid peroxidation and iron dysregulation in the process...Notably, pharmacological SGK1 inhibition sensitizes HGSOC xenograft models to ferroptosis induction, highlighting its therapeutic potential. These findings establish SGK1 as a critical regulator of ferroptosis and suggest targeting SGK1 alongside ferroptosis pathways as a potential therapeutic strategy for HGSOC patients.

Using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines, our data set identified 60 high and 19 moderate confidence hits which induced cancer cell specific cytotoxicity at the lowest compound dose assessed (0.1 µM). We also revealed a series of known (mTOR/PI3K/AKT) and novel (EGFR and MDM2-p53) drug classes in which LGSOC cell lines showed demonstrable susceptibility to.

P2, N=34, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2025 --> Sep 2024 | Trial primary completion date: Apr 2025 --> Sep 2024

P2, N=134, Completed, Imperial College London | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Nov 2023 | Trial primary completion date: Dec 2022 --> Nov 2023

Given the plasticity of TAMs we studied the effects of carboplatin on macrophage phenotypes using both THP-1- and peripheral blood mononuclear cell (PBMC)- derived macrophages and whether this supports CSCs and ovarian cancer progression following treatment...This study supports a role for platinum-based chemotherapies in promoting a transient pro-inflammatory M1-like TAM that enriches for CSCs during treatment. Improving our understanding of TME responses to cytotoxic drugs and identifying novel mechanisms of CSC maintenance will enable the development of better therapeutic strategies for HGSOC.

P=N/A, N=50, Recruiting, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital Hainan Hospital; Hangzhou ZhongMei Huadong Pharmaceutical Co., Ltd.

Analysis of the metabolism of primary HGSOC cells rejects the previously proposed hypothesis that there are distinct groups of HGSOC cells with high and low OXPHOS metabolism that respond differently to glutamine or glucose withdrawal and are characterized by ETC protein levels.