Metabolic dependencies and targets in ovarian cancer.

Simple Summary Aptamers are versatile molecules for cancer treatment. They can be used to target specific molecules, conjugated to additional nucleic acid moieties or payloads. In this review, we will summarize the advancements and challenges related to the use of aptamers for the treatment of ovarian cancer. We will specifically focus on aptamers as therapeutics alone or conjugated to non-coding RNA, nanoparticles, and multivalent aptamers, highlighting their potential as therapeutics by providing an overview of the latest advancements in the field reported in the literature and discussing the main challenges that need to be overcome to improve the effectiveness of aptamers for the treatment of ovarian cancer. Abstract Ovarian cancer (OC) is the most common lethal gynecologic cause of death in women worldwide, with a high mortality rate and increasing incidence. Despite advancements in the treatment, most OC patients still die from their disease due to late-stage diagnosis, the lack of effective diagnostic methods, and relapses. Aptamers, synthetic, short single-stranded oligonucleotides, have emerged as promising anticancer therapeutics. Their ability to selectively bind to target molecules, including cancer-related proteins and receptors, has revolutionized drug discovery and biomarker identification. Aptamers offer unique insights into the molecular pathways involved in cancer development and progression. Moreover, they show immense potential as drug delivery systems, enabling targeted delivery of therapeutic agents to cancer cells while minimizing off-target effects and reducing systemic toxicity. In the context of OC, the integration of aptamers with non-coding RNAs (ncRNAs) presents an opportunity for precise and efficient gene targeting. Additionally, the conjugation of aptamers with nanoparticles allows for accurate and targeted delivery of ncRNAs to specific cells, tissues, or organs. In this review, we will summarize the potential use and challenges associated with the use of aptamers alone or aptamer–ncRNA conjugates, nanoparticles, and multivalent aptamer-based therapeutics for the treatment of OC.

Aptamers as Potential Therapeutic Tools for Ovarian Cancer: Advancements and Challenges

Radiomics and Radiogenomics of Ovarian Cancer: Implications for Treatment Monitoring and Clinical Management.

Resistance to platinum‐based chemotherapy is the major cause of death from high‐grade serous ovarian cancer (HGSOC). We hypothesise that detection of specific DNA methylation changes may predict platinum resistance in HGSOC. Using a publicly available “discovery” dataset we examined epigenomic and transcriptomic alterations between primary platinum‐sensitive (n = 32) and recurrent acquired drug resistant HGSOC (n = 28) and identified several genes involved in immune and chemoresistance‐related pathways. Validation via high‐resolution melt analysis of these findings, in cell lines and HGSOC tumours, demonstrated the most consistent changes were observed in three of the genes: APOBEC3A, NKAPL and PDCD1. Plasma samples from an independent HGSOC cohort (n = 17) were analysed using droplet digital PCR. Hypermethylation of NKAPL was detected in 46% and hypomethylation of APOBEC3A in 69% of plasma samples taken from women with relapsed HGSOC (n = 13), with no alterations identified in disease‐free patients (n = 4). Following these results, and using a CRISPR‐Cas9 approach, we were also able to demonstrate that in vitro NKAPL promoter demethylation increased platinum sensitivity by 15%. Overall, this study demonstrates the importance of aberrant methylation, especially of the NKAPL gene, in acquired platinum resistance in HGSOC.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34496

Unveiling the epigenomic mechanisms of acquired platinum‐resistance in high‐grade serous ovarian cancer

High-grade serous carcinoma (HGSC) is characterized by early abdominal metastasis, leading to a dismal prognosis. In this study, we conducted single-cell RNA sequencing on 109,573 cells from 34 tumor samples of 18 HGSC patients, including both primary tumors and their metastatic sites. Our analysis revealed a distinct S100A9 

Single-cell Transcriptomics Reveals the Aggressive Landscape of High-Grade Serous Carcinoma and Therapeutic Targets in Tumor Microenvironment.

Chromatin accessibility landscape of mouse early embryos revealed by single-cell NanoATAC-seq2.

Single-cell whole-genome sequencing methods have undergone great improvements over the past decade. However, allele dropout, which means the inability to detect both alleles simultaneously in an individual diploid cell, largely restricts the application of these methods particularly for medical applications. Here, we develop a new single-cell whole-genome sequencing method based on third-generation sequencing (TGS) platform named Refresh-seq (restriction fragment ligation-based genome amplification and TGS). It is based on restriction endonuclease cutting and ligation strategy in which two alleles in an individual cell can be cut into equal fragments and tend to be amplified simultaneously. As a new single-cell long-read genome sequencing method, Refresh-seq features much lower allele dropout rate compared with SMOOTH-seq. Furthermore, we apply Refresh-seq to 688 sperm cells and 272 female haploid cells (secondary polar bodies and parthenogenetic oocytes) from F1 hybrid mice. We acquire high-resolution genetic map of mouse meiosis recombination at low sequencing depth and reveal the sexual dimorphism in meiotic crossovers. We also phase the structure variations (deletions and insertions) in sperm cells and female haploid cells with high precision. Refresh-seq shows great performance in screening aneuploid sperm cells and oocytes due to the low allele dropout rate and has great potential for medical applications such as preimplantation genetic diagnosis. 

Mapping crossover events of mouse meiotic recombination by restriction fragment ligation-based Refresh-seq

Integrated analysis of multiomic changes and epigenetic regulation in high-grade serous ovarian cancer provides insights into the molecular characteristics of this disease, which could help improve diagnosis and treatment.

https://aacrjournals.org/cancerres/article-pdf/doi/10.1158/0008-5472.CAN-21-3819/3189652/can-21-3819.pdf

Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer

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Chromatin accessibility landscape of mouse early embryos revealed by single-cell NanoATAC-seq2.

Mapping crossover events of mouse meiotic recombination by restriction fragment ligation-based Refresh-seq

Single-Cell Dissection of the Multiomic Landscape of High-Grade Serous Ovarian Cancer