scholarly journals MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

2019 ◽  
Vol 16 (9) ◽  
pp. 1510 ◽  
Author(s):  
San-Nung Chen ◽  
Renin Chang ◽  
Li-Te Lin ◽  
Chyi-Uei Chern ◽  
Hsiao-Wen Tsai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Messenger Rna ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Female Reproductive System ◽  
Future Perspectives ◽  
Action Current ◽  
Cellular Processes ◽  
New Biomarkers ◽  
Tumor Types

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

scholarly journals Selectins: An Important Family of Glycan-Binding Cell Adhesion Molecules in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2238
Author(s):  
Ayon A. Hassan ◽  
Margarita Artemenko ◽  
Maggie K.S. Tang ◽  
Alice S.T. Wong
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cavity ◽  
Cancer Metastasis ◽  
Cell Interaction ◽  
Gynecological Malignancy ◽  
Selectin Ligand ◽  
Cancer Dissemination ◽  
Tumor Types ◽  
Potential Therapeutic Intervention ◽  
Binding Cell

Ovarian cancer is the most lethal gynecological malignancy worldwide. Unlike most other tumor types that metastasize via the vasculature, ovarian cancer metastasizes predominantly via the transcoelomic route within the peritoneal cavity. As cancer metastasis accounts for the majority of deaths, there is an urge to better understand its determinants. In the peritoneal cavity, tumor-mesothelial adhesion is an important step for cancer dissemination. Selectins are glycan-binding molecules that facilitate early steps of this adhesion cascade by mediating heterotypic cell-cell interaction under hydrodynamic flow. Here, we review the function and regulation of selectins in peritoneal carcinomatosis of ovarian cancer, and highlight how dysregulation of selectin ligand biogenesis affects disease outcome. Further, we will introduce the latest tools in studying selectin-glycan interaction. Finally, an overview of potential therapeutic intervention points that may lead to the development of efficacious therapies for ovarian cancer is provided.

scholarly journals Hereditary Ovarian Cancer: Biology, Response to Chemotherapy and Prognosis

2009 ◽  
Vol 5 (5) ◽  
pp. 543-553 ◽  
Author(s):  
Tamar Safra
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Biology ◽  
Malignant Tumors ◽  
Brca Mutation ◽  
Brca Genes ◽  
Response To Chemotherapy ◽  
Brca Mutation Carriers ◽  
New Biomarkers

Recent evidence has indicated that the prognosis of women with epithelial ovarian cancer who are BRCA-mutation carriers may be better than for noncarriers. Part of the explanation is a higher sensitivity to platinum and other chemotherapies, as was demonstrated in in vitro studies, as well as a possible different biology. BRCA genes are important in double-strand DNA break repair and in other important processes of the cell cycle. Mutation or reduced activity of BRCA genes leads to a higher vulnerability to DNA damage (caused by chemotherapy and radiotherapy) compared with malignant tumors of noncarriers. New targeted drugs, such as poly (ADP-ribose) polymerase-1 and −2 inhibitors, are currently under investigation, as are new biomarkers that will hopefully lead the way to better treatment and longer survival. Testing for the BRCA mutation should be carried out and used as a guide for therapy in most patients with epithelial ovarian cancer.

scholarly journals Functional Roles of Calreticulin in Cancer Biology

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yi-Chien Lu ◽  
Wen-Chin Weng ◽  
Hsinyu Lee
Keyword(s):  
Cell Adhesion ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Cell Types ◽  
Tumor Formation ◽  
Cancer Cell Proliferation ◽  
Transmembrane Receptors ◽  
Functional Roles ◽  
Cellular Processes ◽  
Endoplasmic Reticulum Chaperone

Calreticulin is a highly conserved endoplasmic reticulum chaperone protein which participates in various cellular processes. It was first identified as a Ca2+-binding protein in 1974. Accumulated evidences indicate that calreticulin has great impacts for the development of different cancers and the effect of calreticulin on tumor formation and progression may depend on cell types and clinical stages. Cell surface calreticulin is considered as an “eat-me” signal and promotes phagocytic uptake of cancer cells by immune system. Moreover, several reports reveal that manipulation of calreticulin levels profoundly affects cancer cell proliferation and angiogenesis as well as differentiation. In addition to immunogenicity and tumorigenesis, interactions between calreticulin and integrins have been described during cell adhesion, which is an essential process for cancer metastasis. Integrins are heterodimeric transmembrane receptors which connect extracellular matrix and intracellular cytoskeleton and trigger inside-out or outside-in signaling transduction. More and more evidences reveal that proteins binding to integrins might affect integrin-cytoskeleton interaction and therefore influence ability of cell adhesion. Here, we reviewed the biological roles of calreticulin and summarized the potential mechanisms of calreticulin in regulating mRNA stability and therefore contributed to cancer metastasis.

Targeting Never-In-Mitosis-A Related Kinase 5 in Cancer: A Review

2021 ◽  
Vol 28 ◽  
Author(s):  
Margarite D. Matossian ◽  
Carrow I. Wells ◽  
William J. Zuercher ◽  
Bridgette M. Collins-Burow ◽  
David H. Drewry ◽  
...  
Keyword(s):  
Cancer Biology ◽  
Current Knowledge ◽  
Tumor Development ◽  
Mitotic Kinases ◽  
Cellular Processes ◽  
Physiologic Function ◽  
Therapeutic Development ◽  
Cell Processes ◽  
Tumor Types ◽  
Pharmacologic Inhibition

: Mitotic kinases have integral roles in cell processes responsible for cancer development and progression in all tumor types and are common targets for therapeutics. However, a large subset of the human kinome remains unexplored with respect to functionality in cancer systems. Within the mitotic kinases, the never-in-mitosis kinase (NEK) family, are emerging as novel kinase targets in various cancer types. NEK5 is an understudied member of the NEK family. While there are more recent studies describing physiologic function of NEK5, its role in cancer biology remains widely understudied. However, emerging studies implicate NEK5 has potentially crucial functions in various solid tumors. In this review we discuss current knowledge regarding a role for NEK5 in cancer, and implications of NEK5 expression and activity in tumor development and metastasis. We summarize current studies that examine NEK5 activity in diverse cancer systems and cellular processes. As an understudied kinase, there are currently no selective NEK5-targeting agents to test effects of pharmacologic inhibition in cancer, although there exist recent advancements in this area. Here we also include an update on efforts to develop selective pharmacologic inhibition of NEK5 and we discuss the current direction of NEK5-targeting therapeutic development. Generation of selective NEK5 inhibitors are promising new targeted therapies for cancer growth and metastasis.

ROLE OF ULTRASOUND IN THE DETECTION OF RECURRENT OVARIAN CANCER

2020 ◽  
Vol 6 (1) ◽  
pp. 23-31
Author(s):  
M. Alisherova ◽  
◽  
M. Ismailova
Keyword(s):  
Ovarian Cancer ◽  
Surgical Treatment ◽  
Reproductive System ◽  
Malignant Tumors ◽  
Recurrent Ovarian Cancer ◽  
Primary Diagnosis ◽  
Female Reproductive System

Currently, there are no standard approaches to monitoring patients with ovarian cancer (OC). While the role of ultrasound (US) has been identified in the primary diagnosis of OS, it is still controversial during the subsequent surgical treatment of OC. In world statistics, ovarian cancer is consistently among the four main localizations of malignant tumors of the female reproductive system, along with tumors of the breast, body and cervix.

Targeting Membrane Receptors of Ovarian Cancer Cells for Therapy

2019 ◽  
Vol 19 (6) ◽  
pp. 449-467
Author(s):  
Zhiquan Liang ◽  
Ziwen Lu ◽  
Yafei Zhang ◽  
Dongsheng Shang ◽  
Ruyan Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Receptor Binding ◽  
Cytoreductive Surgery ◽  
Therapeutic Strategies ◽  
Membrane Receptors ◽  
Ovarian Cancer Cells ◽  
Advanced Stage ◽  
Targeted Therapeutics ◽  
Cellular Processes

Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, survival has improved little over the last 20 years. The management of patients with ovarian cancer also remains similar despite studies showing striking differences and heterogeneity among different subtypes. It is therefore clear that novel targeted therapeutics are urgently needed to improve clinical outcomes for ovarian cancer. To that end, several membrane receptors associated with pivotal cellular processes and often aberrantly overexpressed in ovarian cancer cells have emerged as potential targets for receptor-mediated therapeutic strategies including specific agents and multifunctional delivery systems based on ligand-receptor binding. This review focuses on the profiles and potentials of such strategies proposed for ovarian cancer treatment and imaging.

scholarly journals LncRNA SPOCD1-AS from ovarian cancer extracellular vesicles remodels mesothelial cells to promote peritoneal metastasis via interacting with G3BP1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Conghui Wang ◽  
Jiaying Wang ◽  
Xiameng Shen ◽  
Mingyue Li ◽  
Yongfang Yue ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Extracellular Vesicles ◽  
Peritoneal Metastasis ◽  
Cancer Metastasis ◽  
Cancer Therapeutics ◽  
Mesothelial Cells ◽  
Ovarian Cancer Cells ◽  
Adhesion Assay ◽  
Mesenchymal Transition

Abstract Background Metastasis is the key cause of death in ovarian cancer patients. To figure out the biological nature of cancer metastasis is essential for developing effective targeted therapy. Here we investigate how long non-coding RNA (lncRNA) SPOCD1-AS from ovarian cancer extracellular vesicles (EVs) remodel mesothelial cells through a mesothelial-to-mesenchymal transition (MMT) manner and facilitate peritoneal metastasis. Methods EVs purified from ovarian cancer cells and ascites of patients were applied to mesothelial cells. The MMT process of mesothelial cells was assessed by morphology observation, western blot analysis, migration assay and adhesion assay. Altered lncRNAs of EV-treated mesothelial cells were screened by RNA sequencing and identified by qRT-PCR. SPOCD1-AS was overexpressed or silenced by overexpression lentivirus or shRNA, respectively. RNA pull-down and RNA immunoprecipitation assays were conducted to reveal the mechanism by which SPOCD1-AS remodeled mesothelial cells. Interfering peptides were synthesized and applied. Ovarian cancer orthotopic implantation mouse model was established in vivo. Results We found that ovarian cancer-secreted EVs could be taken into recipient mesothelial cells, induce the MMT phenotype and enhance cancer cell adhesion to mesothelial cells. Furthermore, SPOCD1-AS embedded in ovarian cancer-secreted EVs was transmitted to mesothelial cells to induce the MMT process and facilitate peritoneal colonization in vitro and in vivo. SPOCD1-AS induced the MMT process of mesothelial cells via interacting with G3BP1 protein. Additionally, G3BP1 interfering peptide based on the F380/F382 residues was able to block SPOCD1-AS/G3BP1 interaction, inhibit the MMT phenotype of mesothelial cells, and diminish peritoneal metastasis in vivo. Conclusions Our findings elucidate the mechanism associated with EVs and their cargos in ovarian cancer peritoneal metastasis and may provide a potential approach for metastatic ovarian cancer therapeutics.

scholarly journals Glycomic-Based Biomarkers for Ovarian Cancer: Advances and Challenges

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 643
Author(s):  
Francis Mugeni Wanyama ◽  
Véronique Blanchard
Keyword(s):  
Ovarian Cancer ◽  
Survival Rates ◽  
Post Translational Modification ◽  
Diagnostic Biomarkers ◽  
Diagnostic Strategies ◽  
Delay In Diagnosis ◽  
Common Causes ◽  
New Biomarkers ◽  
Cure Rates ◽  
Developed World

Ovarian cancer remains one of the most common causes of death among gynecological malignancies afflicting women worldwide. Among the gynecological cancers, cervical and endometrial cancers confer the greatest burden to the developing and the developed world, respectively; however, the overall survival rates for patients with ovarian cancer are worse than the two aforementioned. The majority of patients with ovarian cancer are diagnosed at an advanced stage when cancer has metastasized to different body sites and the cure rates, including the five-year survival, are significantly diminished. The delay in diagnosis is due to the absence of or unspecific symptoms at the initial stages of cancer as well as a lack of effective screening and diagnostic biomarkers that can detect cancer at the early stages. This, therefore, provides an imperative to prospect for new biomarkers that will provide early diagnostic strategies allowing timely mitigative interventions. Glycosylation is a protein post-translational modification that is modified in cancer patients. In the current review, we document the state-of-the-art of blood-based glycomic biomarkers for early diagnosis of ovarian cancer and the technologies currently used in this endeavor.

scholarly journals ROS and TGFβ: from pancreatic tumour growth to metastasis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Chao-Hui Chang ◽  
Siim Pauklin
Keyword(s):  
Tumour Growth ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Cancer Therapeutics ◽  
Transforming Growth Factor Β ◽  
Ductal Adenocarcinoma ◽  
Cellular Processes ◽  
Tumour Development ◽  
Pancreatic Tumour ◽  
Tgfβ Signalling

AbstractTransforming growth factor β (TGFβ) signalling pathway switches between anti-tumorigenic function at early stages of cancer formation and pro-tumorigenic effects at later stages promoting cancer metastasis. A similar contrasting role has been uncovered for reactive oxygen species (ROS) in pancreatic tumorigenesis. Down-regulation of ROS favours premalignant tumour development, while increasing ROS level in pancreatic ductal adenocarcinoma (PDAC) enhances metastasis. Given the functional resemblance, we propose that ROS-mediated processes converge with the spatial and temporal activation of TGFβ signalling and thereby differentially impact early tumour growth versus metastatic dissemination. TGFβ signalling and ROS could extensively orchestrate cellular processes and this concerted function can be utilized by cancer cells to facilitate their malignancy. In this article, we revisit the interplay of canonical and non-canonical TGFβ signalling with ROS throughout pancreatic tumorigenesis and metastasis. We also discuss recent insight that helps to understand their conflicting effects on different stages of tumour development. These considerations open new strategies in cancer therapeutics.

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