The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

Yan, Shunfei; Frank, Daniel; Son, Jinbae; Hannan, Katherine M.; Hannan, Ross D.; Chan, Keefe T.; Pearson, Richard B.; Sanij, Elaine

doi:10.3390/ijms18010210

Cited by 22 publications

(24 citation statements)

References 121 publications

(162 reference statements)

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“…Despite ongoing efforts to find effective treatment methods for OC, the overall survival rate remains less than 30%, which was mainly caused by the difficulty for early diagnosis, and often results in a poor prognosis [6,7]. Serous ovarian cancer (SOC) is a distinct histological subtype of OC, which is usually diagnosed at advanced stage [8]. Although chemotherapy is the established treatment for SOC, the survival rate remains low, and it is highly anticipated that new treatments will be successfully developed [9,10].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

Wang

Yue³

et al. 2019

J Ovarian Res

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Ovarian cancer (OC) is a type of gynaecological malignancy with high mortality in females. Serous ovarian cancer (SOC) is a distinct subtype of OC with poor early diagnosis. Given the limitations of traditional therapies, such as chemotherapy, targeted treatment is therefore a promising therapy to improve the survival rate of SOC patients. Cyclophilin A (CYPA) is a member of Cyclophilin family and thought to participates in multiple cellular processes such as cell transduction and immune modulation. Recently, various of studies indicated that CYPA has critical impact on cancer progression. CYPA could regulate cell proliferation, invasion, and chemoresistance of multiple types of cancers. However, it is still unclear whether it could affect ovarian cancer. In this study, we demonstrated that CYPA was highly expressed in SOC tissues compared with adjacent tissues. Further, CYPA was significantly associated with clinical stage and lymphnode metastasis of SOC patients. Additionally, data indicated that knockdown of CYPA by its shRNA dramatically reduces migration and invasion capacity of SOC cells in vitro and blocks tumor metastasis in vivo. Our study investigates the involvement of CYPA in the progression and metastasis of SOC, and therefore provides CYPA as a promising therapeutic target for SOC treatment.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

Wang

Yue³

et al. 2019

J Ovarian Res

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“…Non-obese diabetic severe-combined immunodeficiency gamma (NSG) mice (6)(7)(8) week-old female) were purchased from the Garvan Institute (Australian BioResources) and housed in animal cages under standard laboratory conditions.…”

Section: Xenograft Transplantationmentioning

confidence: 99%

“…Increased activation of key oncogenic signalling pathways (PI3K/AKT, RAS/MAPK and MYC) upstream of ribosome biogenesis constitutes an additional hallmark of HGSC 6 , and we hypothesise that inhibiting ribosome biogenesis with the ribosomal RNA gene (rDNA) transcription inhibitor CX-5461 can provide an effective cancer therapeutic option 7 . Indeed, we have shown encouraging responses in a Phase I clinical trial in haematological malignancies 8 , and Canadian trials in breast cancer are ongoing 9 .…”

Section: Introductionmentioning

confidence: 99%

Targeting RNA Polymerase I transcription synergises with TOP1 inhibition in potentiating the DNA damage response in high-grade serous ovarian cancer

Yan

Madhamshettiwar

Simpson

et al. 2019

Preprint

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Limited effective therapeutic options are available for patients with recurrent highgrade serous carcinoma (HGSC), the most common histological subtype accounting for the majority of ovarian cancer deaths. We have shown efficacy in poly-ADP ribose polymerase (PARP) inhibitor-resistant HGSC for the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 through its ability to activate a nucleolar-associated DNA damage response (DDR). Here, we screen the protein-coding genome to identify potential targets whose inhibition enhances the efficacy of CX-5461. We identify a network of cooperating inhibitory interactions, including components of homologous recombination (HR) DNA repair and DNA topoisomerase 1 (TOP1). We highlight that CX-5461 combined with topotecan, a TOP1 inhibitor used as salvage therapy in HGSC, induces robust cell cycle arrest and cell death in a panel of HRproficient HGSC cell lines. The combination potentiates a nucleolar-associated DDR via recruitment of phosphorylated replication protein A (RPA) and ataxia telangiectasia and Rad3 related protein (ATR). CX-5461 plus low-dose topotecan cooperate to potently inhibit xenograft tumour growth, indicating the potential for this strategy to improve salvage therapeutic regimens to treat HGSC.

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“…OC, one of the deadliest malignancies of female reproductive system, is usually diagnosed at progressive stages and is characterized by resistance to standard chemotherapies . Even with developments in diagnostic practices, the 5‐year survival rate is only ∼30% .…”

Section: Discussionmentioning

confidence: 99%

Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

Noreen

Gardner

Fatima

et al. 2020

Proteomics Clinical Apps

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Purpose An early and accurate diagnosis of ovarian carcinoma (OC) may reduce morbidity and mortality of the patients. To improve the clinical outcome in OC patients, the present study is aimed at identifying robust biomarkers for early OC diagnosis. Experimental Design In order to look for early‐stage protein markers, a systematic protein profiling approach involving 2‐dimensional electrophoresis coupled with mass spectrometric analyses of human malignant and non‐malignant ovarian biopsy samples, is performed. Results Six 2D gel spots, corresponding to five proteins, display statistically significant differential expression in the tumor tissues compared to benign controls (FDR ≤ 0.05; PMF score ≥ 79). Ingenuity pathway analysis predicts two proteins, that is, Ca2+‐dependent membrane‐binding protein annexin A6 (AnxA6) and the metabolic enzyme l‐lactate dehydrogenase A chain, as potential predictive biomarkers. Increased expression of AnxA6 is further ascertained by Western blot and enzyme linked immunosorbent assay in the resected tissues and the plasma samples. The expression is found markedly increasing particularly in the advanced stage tumors. Conclusions and Clinical Relevance The significant upregulation of AnxA6 in OC, reported for the first time, is likely to provide insight into the mechanism of OC progression, which may lead to the design of potential diagnostic and therapeutic strategies.

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The Potential of Targeting Ribosome Biogenesis in High-Grade Serous Ovarian Cancer

Cited by 22 publications

References 121 publications

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

RETRACTED ARTICLE: CYPA promotes the progression and metastasis of serous ovarian cancer (SOC) in vitro and in vivo

Targeting RNA Polymerase I transcription synergises with TOP1 inhibition in potentiating the DNA damage response in high-grade serous ovarian cancer

Upregulated Expression of Calcium‐Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma

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