Drug resistance in ovarian cancer: from mechanism to clinical trial

Wang, Ling; Wang, Xin; Zhu, Xueping; Zhong, Lin; Jiang, Qingxiu; Wang, Ya; Tang, Qin; Li, Qiaoling; Zhang, Cong; Wang, Haixia; Zou, Dongling

doi:10.1186/s12943-024-01967-3

Cited by 23 publications

(2 citation statements)

References 238 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Drug resistance is a bottleneck in ovarian cancer treatment despite the application of new drugs. A profound understanding of the mechanisms of resistance is necessary to solve this problem [7]. The main mechanisms of resistance are disorders in transmembrane transport and in DNA damage repair, the dysregulation of cancerassociated signaling pathways, and epigenetic modifications such as DNA methylation, histone modifications, and non-coding RNA activity.…”

Section: Introductionmentioning

confidence: 99%

Activity of NAD(P)H-Oxidoreductases in Ovarian Cancer

Fedorova,

Voznesensky,

Sosnova

et al. 2024

Biomedicines

View full text Add to dashboard Cite

Reactive oxygen species (ROS) play an important and controversial role in carcinogenesis. Microsomal redox chains containing NADH- and NADPH-dependent oxidoreductases are among the main sites of intracellular ROS synthesis, but their role in the oxidative balance has not been fully studied. Here, we studied the activity of cytochrome b5 reductase (CYB5R) and cytochrome P450 reductase (CYPOR) in ovarian cancer tissues and cells isolated from peritoneal fluid, along with the antioxidant capacity of peritoneal fluid. We used the developed a chemiluminescence assay based on stimulation with NADH and NADPH, which reflects the activity of CYB5R and CYPOR, respectively. The activity of CYB5R and CYPOR was significantly higher in moderately and poorly differentiated ovarian adenocarcinomas compared with well-differentiated adenocarcinomas and cystadenomas. For the chemotherapy-resistant tumors, the activity of tissue CYB5R and CYPOR was lower compared to the non-resistant tumors. In the peritoneal fluid, the antioxidant capacity significantly increased in this series, benign tumors < well-differentiated < moderately and poorly differentiated adenocarcinomas, so the antioxidant excess was observed for moderately and poorly differentiated adenocarcinomas. The antioxidant capacity of peritoneal fluid and the activity of CYB5R and CYPOR of cells isolated from peritoneal fluid were characterized by a direct moderate correlation for moderately and poorly differentiated adenocarcinomas. These results indicate the significant role of NAD(P)H oxidoreductases and the antioxidant potential of peritoneal fluid in cancer biochemistry. The parameters studied are useful for diagnostics and prognostics. The developed assay can be used to analyze CYB5R and CYPOR activity in other tissues and cells.

show abstract

Section: Introductionmentioning

confidence: 99%

Activity of NAD(P)H-Oxidoreductases in Ovarian Cancer

Fedorova,

Voznesensky,

Sosnova

et al. 2024

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Ovarian cancer (OC) is a prevalent form of gynecological cancer, recognized for its aggressive nature and tendency to metastasize ( 1 ). Its atypical presentation poses challenges for early detection and treatment, with approximately three-quarters of OC cases diagnosed at an advanced stage ( 2 ). OC includes various types, including epithelial tumors, sex cord stromal tumors, germ cell tumors, unclassified types, and metastatic secondary tumors, with epithelial ovarian cancer (EOC) accounting for over 95% of cases ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Recent advances in understanding the immune microenvironment in ovarian cancer

Chen,

Yang,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

The occurrence of ovarian cancer (OC) is a major factor in women’s mortality rates. Despite progress in medical treatments, like new drugs targeting homologous recombination deficiency, survival rates for OC patients are still not ideal. The tumor microenvironment (TME) includes cancer cells, fibroblasts linked to cancer (CAFs), immune-inflammatory cells, and the substances these cells secrete, along with non-cellular components in the extracellular matrix (ECM). First, the TME mainly plays a role in inhibiting tumor growth and protecting normal cell survival. As tumors progress, the TME gradually becomes a place to promote tumor cell progression. Immune cells in the TME have attracted much attention as targets for immunotherapy. Immune checkpoint inhibitor (ICI) therapy has the potential to regulate the TME, suppressing factors that facilitate tumor advancement, reactivating immune cells, managing tumor growth, and extending the survival of patients with advanced cancer. This review presents an outline of current studies on the distinct cellular elements within the OC TME, detailing their main functions and possible signaling pathways. Additionally, we examine immunotherapy rechallenge in OC, with a specific emphasis on the biological reasons behind resistance to ICIs.

show abstract

New S‐substituted‐3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4(3H)‐one scaffold with promising anticancer activity profile through the regulation and inhibition of mutated B‐RAF signaling pathway

Seif,

Wardakhan,

Hassan

et al. 2024

Drug Development Research

View full text Add to dashboard Cite

Novel 3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidine derivatives were synthesized and screened for their antiproliferative activity against a panel of 60 cancer cell lines. Derivatives 5b, 5f, and 9c showed significant antitumor activity at a single dose with mean growth inhibition of 55.62%, 55.79%, and 71.40%, respectively. These compounds were further investigated against HCT‐116, colon cancer cell line, and FHC, normal colon cell line. Compound 9c showed the highest activity with IC50 = 0.904 ± 0.03 µM and SI = 20.42 excelling doxorubicin which scored IC50 = 2.556 ± 0.09 µM and SI = 6.19. Compound 9c was also the most potent against B‐RAFWT and mutated B‐RAFV600E with IC50 = 0.145 ± 0.005 and 0.042 ± 0.002 µM, respectively in comparison with vemurafenib with IC50 = 0.229 ± 0.008 and 0.038 ± 0.001 µM, respectively. The cell cycle analysis showed that 9c increased the cell population and induced an arrest in the cell cycle of HCT‐116 cancer cells at the G0‐G1 stage with 1.23‐fold. Apoptosis evaluation showed that compound 9c displayed an 18.18‐fold elevation in total apoptosis of HCT‐116 cancer cells in comparison to the control. Compound 9c increased the content of caspase‐3 by 3.52‐fold versus the control. A molecular modeling study determined the binding profile and interaction of 9c with the B‐RAF active site.

show abstract

Drug resistance in ovarian cancer: from mechanism to clinical trial

Cited by 23 publications

References 238 publications

Activity of NAD(P)H-Oxidoreductases in Ovarian Cancer

Activity of NAD(P)H-Oxidoreductases in Ovarian Cancer

Recent advances in understanding the immune microenvironment in ovarian cancer

New S‐substituted‐3‐phenyltetrahydrobenzo[4,5]thieno[2,3‐d]pyrimidin‐4(3H)‐one scaffold with promising anticancer activity profile through the regulation and inhibition of mutated B‐RAF signaling pathway

Contact Info

Product

Resources

About