Genetic landscape of homologous recombination repair and practical outcomes of PARPi therapy in ovarian cancer management.

Background: Genetic studies of ovarian cancer (OC) have historically focused on BRCA1/2 mutations, lacking other studies of homologous recombination repair (HRR). Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit synthetic lethality to significantly improve OC treatment outcomes, especially in BRCA1/2 deficiency patients. Objectives: Our study aims to construct a mutation map of HRR genes in OC and identify factors influencing the efficacy of PARPi. Design: A retrospective observational analysis of HRR gene variation data from 695 OC patients from March 2019 to February 2022 was performed. Methods: The HRR gene variation data of 695 OC patients who underwent next-generation sequencing (NGS) in the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Clinical data on the use of PARPi in these patients were also gathered to identify factors that may interfere with the efficacy of PARPi. Results: Out of 127 pathogenic variants in the BRCA1/2 genes, 104 (81.9%) were BRCA1 mutations, and 23 (18.1%) were BRCA2 mutations. Among the 59 variants of uncertain significance (VUS), 20 (33.9%) were BRCA1, while 39 (66.1%) were BRCA2 mutations. In addition to BRCA1/2, HRR gene results showed that 9 (69%) of 13 were HRR pathway pathogenic variants; and 16 (1.7%) of 116 VUS were Food and Drug Administration (FDA)-approved mutated HRR genes. Notably, the treatment regimen significantly influenced the effectiveness of PARPi, especially when using first-line maintenance therapy, leading to enhanced progression-free survival (PFS) compared to alternative protocols. Conclusion: Focusing on HRR gene mutations and supporting clinical research about PARPi in OC patients is crucial for developing precision treatment strategies and enhancing prognosis.

Exploration of organoids in ovarian cancer: From basic research to clinical translation.

Ovarian cancer is a highly heterogeneous tumor with a poor prognosis. The lack of reliable and efficient research models that can accurately mimic heterogeneity has impeded in-depth investigations and hindered the clinical translation of research findings in ovarian cancer. Organoid models have emerged as a promising in vitro approach, demonstrating remarkable fidelity to the histological, molecular, genomic, and transcriptomic features of their tissues of origin. In recent years, organoids have contributed to advancing our understanding of ovarian cancer initiation, metastasis, and drug resistance mechanisms, as well as facilitating clinical screening of effective therapeutic agents. The establishment of high-throughput organoid culture systems, coupled with cutting-edge technologies such as organ-on-a-chip, genetic engineering, and 3D printing, has tremendous potential for accelerating ovarian cancer research translation. In this review, we present a comprehensive overview of the latest exploration of organoids in basic ovarian cancer research and clinical translation. Furthermore, we discuss the prospects and challenges associated with the use of organoids and related novel technologies in the context of ovarian cancer. This review provides insights into the application of organoids in ovarian cancer.

Aldolase A promotes cervical cancer cell radioresistance by regulating the glycolysis and DNA damage after irradiation.

Radioresistance is the major obstacle that affects the efficacy of radiotherapy which is an important treatment for cervical cancer. By analyzing the databases, we found that aldolase A (ALDOA), which is a key enzyme in metabolic reprogramming, has a higher expression in cervical cancer patients and is associated with poor prognosis. We detected the expression of ALDOA in the constructed cervical cancer radioresistance (RR) cells by repetitive irradiation and found that it was upregulated compared to the control cells. Functional assays were conducted and the results showed that the knockdown of ALDOA in cervical cancer RR cells inhibited the proliferation, migration, and clonogenic abilities by regulating the cell glycolysis. In addition, downregulation of ALDOA enhanced radiation-induced apoptosis and DNA damage by causing G2/M phase arrest and further promoted radiosensitivity of cervical cancer cells. The functions of ALDOA in regulating tumor radiosensitivity were also verified by the mouse tumor transplantation model in vivo. Therefore, our study provides new insights into the functions of ALDOA in regulating the efficacy of radiotherapy and indicates that ALDOA might be a promising target for enhancing radiosensitivity in treating cervical cancer patients.

Treatment strategies for intrauterine adhesion: focus on the exosomes and hydrogels.

Intrauterine adhesion (IUA), also referred to as Asherman Syndrome (AS), results from uterine trauma in both pregnant and nonpregnant women. The IUA damages the endometrial bottom layer, causing partial or complete occlusion of the uterine cavity. This leads to irregular menstruation, infertility, or repeated abortions. Transcervical adhesion electroreception (TCRA) is frequently used to treat IUA, which greatly lowers the prevalence of adhesions and increases pregnancy rates. Although surgery aims to disentangle the adhesive tissue, it can exacerbate the development of IUA when the degree of adhesion is severer. Therefore, it is critical to develop innovative therapeutic approaches for the prevention of IUA. Endometrial fibrosis is the essence of IUA, and studies have found that the use of different types of mesenchymal stem cells (MSCs) can reduce the risk of endometrial fibrosis and increase the possibility of pregnancy. Recent research has suggested that exosomes derived from MSCs can overcome the limitations of MSCs, such as immunogenicity and tumorigenicity risks, thereby providing new directions for IUA treatment. Moreover, the hydrogel drug delivery system can significantly ameliorate the recurrence rate of adhesions and the intrauterine pregnancy rate of patients, and its potential mechanism in the treatment of IUA has also been studied. It has been shown that the combination of two or more therapeutic schemes has broader application prospects; therefore, this article reviews the pathophysiology of IUA and current treatment strategies, focusing on exosomes combined with hydrogels in the treatment of IUA. Although the use of exosomes and hydrogels has certain challenges in treating IUA, they still provide new promising directions in this field.

Characterization of fecal microbiota in cervical cancer patients associated with tumor stage and prognosis.

Cervical cancer (CC) is the fourth most frequent malignancy among women worldwide, and its prevention and treatment are evolving rapidly. The gut microbiota has been reported to play a crucial role both in the preservation of homeostasis and the development of cervical cancer. In this study, we collected fecal samples to investigate the microbial signatures in cervical cancer patients compared with healthy controls using 16S rRNA sequencing analysis and metagenomic next-generation sequencing (mNGS) testing. Our findings demonstrated a substantial difference in the gut microbiota composition of cervical cancer patients and healthy controls. The disease and stage were most significantly negatively correlated with Ruminococcus 2, which might be considered a potential clinically relevant biomarker. Functions of differential microbiomes were also analyzed, indicating significant differences in metabolisms and biosynthesis between the two groups. These findings demonstrate that patients with cervical cancer have certain species of gut microbiota that are exclusive to them and particular species have the potential to be used in the prognosis of cervical cancer.

Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance.

Radiotherapy is widely used as an indispensable treatment option for cervical cancer patients. However, radioresistance always occurs and has become a big obstacle to treatment efficacy. The reason for radioresistance is mainly attributed to the high repair ability of tumor cells that overcome the DNA damage caused by radiotherapy, and the increased self-healing ability of cancer stem cells (CSCs). Accumulating findings have demonstrated that the tumor microenvironment (TME) is closely related to cervical cancer radioresistance in many aspects, especially in the metabolic processes. In this review, we discuss radiotherapy in cervical cancer radioresistance, and focus on recent research progress of the TME metabolism that affects radioresistance in cervical cancer. Understanding the mechanism of metabolism in cervical cancer radioresistance may help identify useful therapeutic targets for developing novel therapy, overcome radioresistance and improve the efficacy of radiotherapy in clinics and quality of life of patients.

Bioinformatics analysis of the role of aldolase A in tumor prognosis and immunity.

Aldolase A (ALDOA) is an enzyme that plays an important role in glycolysis and gluconeogenesis, which is closely related to tumor metabolism. In this study, the overall roles of ALDOA in pan-cancer have been investigated from several aspects using databases and online analysis tools. Using the ONCOMINE database, the expression of ALDOA in various cancers was analyzed. The prognostic role of ALDOA was explored by PrognoScan, GEPIA, and Kaplan-Meier Plotter. The immune-related role of ALDOA and its downstream substrates was decided by TIMER, cBioPortal and String. Our data indicate that ALDOA expression level in lung adenocarcinoma, liver hepatocellular carcinoma, head and neck squamous cell carcinoma is higher than that in normal tissues. Increased expression of ALDOA often indicates a poor prognosis for patients. The correlation between ALDOA and immune infiltration among different tumors is very different. We also investigate the relationship between ALDOA and its upstream/downstream proteins. Our results showed that ALDOA could be used as a biomarker for the tumor prognosis, and could be correlated with the infiltrating levels of macrophages, CD4+ T cells and CD8+ T cells.