Ovarian cancer treatment summary

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors...

OBJECTIVES: This retrospective study aims to evaluating the subsequent management and outcomes after first-line PARPi progression in Chinese ovarian cancer population. METHODS: Clinical and pathologic variables, treatment modalities, and outcomes were assessed. We investigated the subsequent management and outcomes after first-line PARPi progression. The objective response rate (ORR) and disease control rate (DCR) parameters were evaluated to determine the response to subsequent chemotherapy...

Ovarian cancer is a malignant tumor that seriously endangers the lives of women, with chemotherapy being the primary clinical treatment. However, chemotherapy encounters the problem of generating multidrug resistance (MDR), mainly due to drug efflux induced by P-glycoprotein (P-gp), which decreases intracellular accumulation of chemotherapeutic drugs. The drugs efflux mediated by P-gp requires adenosine triphosphate (ATP) hydrolysis to provide energy. Therefore, modulating energy metabolism pathways and inhibiting ATP production may be a potential strategy to reverse MDR...

WHAT IS THIS SUMMARY ABOUT?: This PLSP provides a short summary of an original scientific article that presented results from the PRIMA study after 3.5 years of follow-up time. The original article was published in the European Journal of Cancer in 2023. The PRIMA study included adult patients with newly diagnosed advanced high-risk ovarian cancer whose tumors shrunk or became undetectable after treatment with chemotherapy with or without surgery. The PRIMA study evaluated how well the drug niraparib, also known as Zejula, worked at delaying or preventing ovarian cancer from coming back (recurring) or getting worse (progressing) compared with placebo (a substance with no effects that a doctor gives to a patient instead of a drug)...

In cancer, genetic and transcriptomic variations generate clonal heterogeneity, possibly leading to treatment resistance. Long-read single-cell RNA sequencing (LR scRNA-seq) has the potential to detect genetic and transcriptomic variations simultaneously. Here, we present LongSom, a computational workflow leveraging LR scRNA-seq data to call de novo somatic single-nucleotide variants (SNVs), copy-number alterations (CNAs), and gene fusions to reconstruct the tumor clonal heterogeneity. For SNV calling, LongSom distinguishes somatic SNVs from germline polymorphisms by reannotating marker gene expression-based cell types using called variants and applying strict filters...

Observational studies have previously reported an association between depression and certain female reproductive disorders. However, the causal relationships between depression and different types of female reproductive disorders remain unclear in terms of direction and magnitude. We conducted a comprehensive investigation using a two-sample bi-directional Mendelian randomization analysis, incorporating publicly available GWAS summary statistics. Our aim was to establish a causal relationship between genetically predicted depression and the risk of various female reproductive pathological conditions, such as ovarian dysfunction, polycystic ovary syndrome(PCOS), ovarian cysts, abnormal uterine and vaginal bleeding(AUB), endometriosis, leiomyoma of the uterus, female infertility, spontaneous abortion, eclampsia, pregnancy hypertension, gestational diabetes, excessive vomiting in pregnancy, cervical cancer, and uterine/endometrial cancer...

BACKGROUND: Ovarian carcinoma is an aggressive gynecological malignancy. Kirenol, a diterpene compound, has recently gained attention for its potential anticancer properties. However, its exact anti-tumor mechanism remains largely unexplored. OBJECTIVE: In this study, we explored the inhibitory effects of Kirenol on ovarian cancer using network pharmacology and in vitro experiments and elucidated its underlying mechanisms. METHODS: Through the utilization of molecular docking, we established a network of proteinprotein interactions (PPI), which unveiled CDK4 as an essential target...

Genome-wide sequencing allows for prediction of clinical treatment responses and outcomes by estimating genomic status. Here, we developed Genomic Status scan (GSscan), a long short-term memory (LSTM)-based deep-learning framework, which utilizes low-pass whole genome sequencing (WGS) data to capture genomic instability-related features. In this study, GSscan directly surveys homologous recombination deficiency (HRD) status independent of other existing biomarkers. In breast cancer, GSscan achieved an AUC of 0...

Ovarian cancer poses a significant threat to women's health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer...

INTRODUCTION: Compared with the traditional drug development pathway, investigating alternative uses for existing drugs (ie, drug repurposing) requires substantially less time, cost and resources. Immune checkpoint inhibitors are licensed for the treatment of certain breast, colorectal, head and neck, lung and melanoma cancers. These drugs target immune checkpoint proteins to reduce the suppression of T cell activation by cancer cells. As T cell suppression is a hallmark of cancer common across anatomical sites, we hypothesise that immune checkpoint inhibitors could be repurposed for the treatment of additional cancers beyond the ones already indicated...

Ovarian cancer poses a formidable health challenge for women globally, necessitating innovative therapeutic approaches. This review provides a succinct summary of the current research status on lipid-based nanocarriers in the context of ovarian cancer treatment. Lipid-based nanocarriers, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs), offer a promising solution for delivering anticancer drugs with enhanced therapeutic effectiveness and reduced adverse effects...

Aggresomes are the product of misfolded protein aggregation, and the presence of aggresomes has been correlated with poor prognosis in cancer patients. However, the exact role of aggresomes in tumorigenesis and cancer progression remains largely unknown. Herein, the multiomics screening reveal that OTUD1 protein plays an important role in retaining ovarian cancer stem cell (OCSC) properties. Mechanistically, the elevated OTUD1 protein levels lead to the formation of OTUD1-based cytoplasmic aggresomes, which is mediated by a short peptide located in the intrinsically disordered OTUD1 N-terminal region...

Exploring non-genetic evolution of cell states during cancer treatments has become attainable by recent advances in lineage-tracing methods. However, transcriptional changes that drive cells into resistant fates may be subtle, necessitating high resolution analysis. Here, we present ReSisTrace that uses shared transcriptomic features of sister cells to predict the states priming treatment resistance. Applying ReSisTrace in ovarian cancer cells perturbed with olaparib, carboplatin or natural killer (NK) cells reveals pre-resistant phenotypes defined by proteostatic and mRNA surveillance features, reflecting traits enriched in the upcoming subclonal selection...

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease...

RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies. Currently, no suitable model exists to elucidate the role of RAD51D in disease initiation and progression. Here, we established organoids from primary human FTE and introduced TP53 as well as RAD51D knockdown to enable the exploration of their mutational impact on FTE lesion generation. We observed that TP53 deletion rescued the adverse effects of RAD51D deletion on the proliferation, stemness, senescence, and apoptosis of FTE organoids...

WHAT IS THIS SUMMARY ABOUT?: This document provides a summary of results from the article that evaluated the safety and efficacy of the fixed and individualized starting doses of niraparib in the PRIMA study. The original article was published in the journal Cancer in March 2023. The PRIMA study included adult patients with newly diagnosed advanced ovarian cancer who had finished treatment with chemotherapy and surgery. Once patients entered the study, they were treated with an oral (by mouth) medication called niraparib or placebo (substance with no effects that a doctor gives to a patient instead of a drug)...

Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly selected patients with early stage, low-risk cervical cancer and a tumor size ≤ 2 cm, several treatment strategies can be offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal, or minimally invasive approach and has been shown to have an equivalent oncologic outcome compared to radical hysterectomy...

Ovarian cancer (OC) is a highly heterogeneous disease, with patients at different tumor staging having different survival times. Metabolic reprogramming is one of the key hallmarks of cancer; however, the significance of metabolism-related genes in the prognosis and therapy outcomes of OC is unclear. In this study, we used weighted gene coexpression network analysis and differential expression analysis to screen for metabolism-related genes associated with tumor staging. We constructed the metabolism-related gene prognostic index (MRGPI), which demonstrated a stable prognostic value across multiple clinical trial end points and multiple validation cohorts...

AIM: Telomerase expression is unique to cancer cells, making it a promising target for therapy. However, a major drawback of telomerase inhibition is that it affects cancer cell proliferation only when telomeres shorten, creating a lag phase post-continuous drug treatment. Acute cytotoxicity of telomerase inhibitors is dependent on their ability to induce DNA damage. p53 senses DNA damage and is the primary effector required for sensitizing cells towards apoptosis. MAIN METHODS: Isogenic p53+/+ and p53-/- ovarian cancer cell lines were generated using the CRISPR/Cas9 system and the anti-cancer effect of telomerase inhibitors MST-312 and BIBR1532 were determined...

OBJECTIVES: Breast oncology genetics emerged almost 30 years ago with the discovery of the BRCA1 and BRCA2 genes. The evolution of analytical practices has progressively allowed access to tests whose results now have a considerable impact on the management of both female and male breast cancers.The Sénologie Commission of the Collège National des Gynécologues et Obstétriciens Français (CNGOF) asked five specialists in breast surgery, oncology and oncological genetics to draw up a summary of the oncogenetic testing criteria used and the clinical implications for the female and male population of the test results, with or without an identified causal variant...