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Ovarian cancer target drugs

Rachael R Schulte, Richard H Ho
The organic anion transporting polypeptides (OATPs) are a superfamily of drug transporters involved in the uptake and disposition of a wide array of structurally divergent endogenous and exogenous substrates, including steroid hormones, bile acids, and commonly used drugs, such as anti-infectives, anti-hypertensives, and cholesterol lowering agents. In the past decade, OATPs, primarily OATP1A2, OATP1B1, and OATP1B3, have emerged as potential mediators of chemotherapy disposition, including drugs such as methotrexate, doxorubicin, paclitaxel, docetaxel, irinotecan and its important metabolite SN-38, and certain tyrosine kinase inhibitors...
February 19, 2019: Molecular Pharmacology
Koji Nakamura, Kenjiro Sawada, Mayuko Miyamoto, Yasuto Kinose, Akihiko Yoshimura, Kyoso Ishida, Masaki Kobayashi, Aasa Shimizu, Erika Nakatsuka, Kae Hashimoto, Seiji Mabuchi, Tadashi Kimura
Paclitaxel is a first-line drug for treating epithelial ovarian cancer (EOC). However, prognosis for patients with advanced stage cancer remains poor due to primary or acquired drug resistance. Therefore, overcoming chemoresistance is one of the greatest challenges in treating EOC. In this study, we identified microRNAs (miRNA) that regulate paclitaxel resistance and tested their potential utility as therapeutic targets. Paclitaxel-resistant cell lines were established using two EOC cell lines: SKVO3ip1 and HeyA8...
January 18, 2019: Oncotarget
Ya'nan Yang, Song Li, Yiting Sun, Di Zhang, Zeyi Zhao, Lian Liu
Purpose: Peritoneal metastasis is the most common pathway for the spread of ovarian cancer. Ovarian cancer cells in ascites prefer to aggregate into the more chemoresistant multicellular spheroids (MCSs), leading to treatment failure and disease recurrence. We previously established a suspension MCS model of ovarian cancer cells in vitro and found that the MCS cells acquired drug resistance to cisplatin. In the present study, we aimed to uncover the underlying mechanism of the platinum resistance of MCS and the potential targets to reverse the drug resistance...
2019: OncoTargets and Therapy
Xiaolan Zhu, Huiling Shen, Xinming Yin, Meiling Yang, Hong Wei, Qi Chen, Fan Feng, Yueqin Liu, Wenlin Xu, Yuefeng Li
BACKGROUND: How exosomal microRNAs (miRNAs) derived from macrophages contribute to the development of drug resistance in the context of the hypoxic tumor microenvironment in epithelial ovarian cancer (EOC) remains poorly understood. METHODS: The miRNA levels were detected by qRT-PCR. Protein levels of HIF-1α, CD163 and PTEN-PI3K/AKT pathway were assessed by Western blot (WB) and Immunohistochemistry (IHC). Exosomes were isolated, and then confirmed by Transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA) and WB...
February 15, 2019: Journal of Experimental & Clinical Cancer Research: CR
Łukasz Lamch, Julita Kulbacka, Magda Dubińska-Magiera, Jolanta Saczko, Kazimiera A Wilk
Targeted and effective drug transport is becoming an attractive option in cancer therapy since it can improve drug efficacy and reduce drugs' side effects in normal tissues. In addition to using specific surface ligand molecules, the selective drug delivery can be accomplished via enhanced permeability and retention effect. Therefore, in our studies, we entrapped zinc (II) phthalocyanine (ZnPc) - a second generation photosensitizer - in folate-functionalized micelles of the biocompatible, FDA-approved for biomedical application diblock copolymer methoxypoly(ethylene oxide)-b-poly(L-lactide) (mPEG-b-PLLA) and its derivative with folate (FA) attached to the end of PEG chain (FA-PEG-b-PLLA)...
February 12, 2019: Photodiagnosis and Photodynamic Therapy
Shipeng Gong, Yongning Chen, Fanliang Meng, Yadi Zhang, Huan Wu, Chanyuan Li, Guangping Zhang
Currently, cisplatin (DDP) is the first-line chemotherapeutic agent used for treatment of ovarian cancer, but gradually acquired drug resistance minimizes its therapeutic outcomes. We aimed to identify crucial genes associated with DDP resistance in ovarian cancer and uncover potential mechanisms. Two sets of gene expression data were downloaded from Gene Expression Omnibus, and bioinformatics analysis was conducted. In our study, the differentially expressed genes between DDP-sensitive and DDP-resistant ovarian cancer were screened in GSE15709 and GSE51373 database, and chromosome condensation 2 regulator (RCC2) and nucleoporin 160 were identified as 2 genes that significantly up-regulated in DDP-resistant ovarian cancer cell lines compared with DDP-sensitive cell lines...
February 15, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Maria Bonello, Andrew Harvey Sims, Simon Peter Langdon
Ovarian cancer is the second most lethal gynecological cancer worldwide and while most patients respond to initial therapy, they often relapse with resistant disease. Human epidermal growth factor receptors (especially HER1/EGFR and HER2/ERBB2) are involved in disease progression; hence, strategies to inhibit their action could prove advantageous in ovarian cancer patients, especially in patients resistant to first line therapy. Monoclonal antibodies and tyrosine kinase inhibitors are two classes of drugs that act on these receptors...
November 2018: Cancer Biology & Medicine
Ashok Sharma, Mustafa Albahrani, Wa Zhang, Christina N Kufel, Smitha R James, Kunle Odunsi, David Klinkebiel, Adam R Karpf
The POTE gene family consists of 14 homologous genes localized to autosomal pericentromeres, and a sub-set of POTEs are cancer-testis antigen (CTA) genes. POTEs are over-expressed in epithelial ovarian cancer (EOC), including the high-grade serous subtype (HGSC), and expression of individual POTEs correlates with chemoresistance and reduced survival in HGSC. The mechanisms driving POTE overexpression in EOC and other cancers is unknown. Here, we investigated the role of epigenetics in regulating POTE expression, with a focus on DNA hypomethylation...
February 14, 2019: Epigenetics: Official Journal of the DNA Methylation Society
Huizhu Gan, Lin Lin, Nanjun Hu, Yang Yang, Yu Gao, Yu Pei, Kang Chen, Butong Sun
BACKGROUND: Aspirin, an anti-inflammatory drug, has been widely investigated in the treatment of many cancer types, including colorectal, ovarian, breast, and prostate cancers. MicroRNAs (miRNAs) are the most well studied noncoding RNAs in cancers. In the current study, we were interested in defining the function of aspirin in lung cancer treatment and the related noncoding RNAs involved in this process. METHODS: The function of aspirin in lung cancer growth was evaluated by cell viability and colony formation assays...
February 12, 2019: Thoracic Cancer
Erdem Coskun, Gamze Tuna, Pawel Jaruga, Alessandro Tona, Onur Erdem, Miral Dizdaroglu
Poly(ADP ribose) polymerase 1 (PARP1) is a multifunctional DNA repair protein of the base excision repair pathway and plays a major role in the repair of DNA strand breaks and in replication and transcriptional regulation among other functions. Mounting evidence points to the predictive and prognostic value of PARP1 expression in human cancers. Thus, PARP1 has become an important target in cancer therapy, leading to the development of inhibitors as anticancer drugs. In the past, PARP1 expression levels in tissue samples have generally been estimated by indirect and semi-quantitative immunohistochemical methods...
February 1, 2019: DNA Repair
Pei Wang, Maryam Garza, Meredith Zozus
EHR-based, computable phenotypes can be leveraged by healthcare organizations and researchers to improve the cohort identification process. The ability to identify patient cohorts using aspects of care and outcomes based on clinical characteristics or diagnostic conditions and/or risk factors presents opportunities to researchers targeting specific populations for drug development and disease interventions. The objective of this review was to summarize the literature describing the development and use of phenotypes for cohort identification of cancer patients...
2019: Studies in Health Technology and Informatics
Jing Jin, Wei Xiang, Shuang Wu, Min Wang, Meifang Xiao, Ali Deng
The essential roles of eukaryotic translation initiation factor 4E (eIF4E) have been shown in various cancers, including ovarian cancer. In this work, we demonstrate that eIF4E inhibition in ovarian cancer can be achieved by ribavirin, a FDA-approved antiviral drug. We show that ribavirin at clinically relevant doses significantly inhibits growth and survival in multiple ovarian cancer cell lines, regardless of morphological and molecular subtypes. Mechanistically, ribavirin suppresses Akt/mTOR and eIF4E/p70S6K signaling pathways in ovarian cancer cells...
February 7, 2019: Biochemical and Biophysical Research Communications
Bruna Corradetti, Simone Pisano, Robert Steven Conlan, Mauro Ferrari
Ovarian cancer (OC) is the seventh most common cancer in women worldwide. Standard therapeutic treatments involve debulking surgery combined with platinum-based chemotherapies. Of the patients with advanced stage cancer that initially respond to current treatments 50%-75% relapse. Immunotherapy-based approaches aimed at boosting anti-tumor immunity have recently emerged as promising tools to challenge tumor progression. Treatments with inhibitors of immune checkpoint molecules have shown impressive results in other types of tumors...
February 8, 2019: Journal of Pharmacology and Experimental Therapeutics
Rossella Farra, Barbara Dapas, Mario Grassi, Fabio Benedetti, Gabriele Grassi
No abstract text is available yet for this article.
February 6, 2019: Expert Opinion on Therapeutic Targets
Xiaoyan Hu, Yang Meng, Lian Xu, Lei Qiu, Mingtian Wei, Dan Su, Xu Qi, Ziqiang Wang, Shengyong Yang, Cong Liu, Junhong Han
CRL4, a well-defined E3 ligase, has been reported to be upregulated and is proposed to be a potential drug target in ovarian cancers. However, the biological functions of CRL4 and the underlying mechanism regulating cancer chemoresistance are still largely elusive. Here, we show that CRL4 is considerably increased in cisplatin-resistant ovarian cancer cells, and CRL4 knockdown with shRNAs is able to reverse cisplatin-resistance of ovarian cancer cells. Moreover, CRL4 knockdown markedly inhibits the expression of BIRC3, one of the inhibitors of apoptosis proteins (IAPs)...
February 4, 2019: Cell Death & Disease
Caroline Ladurantie, Mathilde Coustets, Georges Czaplicki, Pascal Demange, Serge Mazères, Stéphanie Dauvillier, Justin Teissié, Marie-Pierre Rols, Alain Milon, Vincent Ecochard, Grégori Gross, Laurent Paquereau
The development of drug delivery and imaging tools is a major challenge in human health, in particular in cancer pathologies. This work describes the optimization of a protein nanocontainer, belonging to the lectin protein family, for its use in epithelial cancer diagnosis and treatment. Indeed, it specifically targets a glycosidic marker, the T antigen, which is known to be characteristic of epithelial cancers. Its quaternary structure reveals a large hydrated inner cavity able to transport small therapeutic molecules...
February 1, 2019: Nanoscale
Shu Z Wiley, Krishna Sriram, Cristina Salmerón, Paul A Insel
GPR68 (or ovarian cancer G protein-coupled receptor 1, OGR1) is a proton-sensing G-protein-coupled receptor (GPCR) that responds to extracellular acidity and regulates a variety of cellular functions. Acidosis is considered a defining hallmark of the tumor microenvironment (TME). GPR68 expression is highly upregulated in numerous types of cancer. Emerging evidence has revealed that GPR68 may play crucial roles in tumor biology, including tumorigenesis, tumor growth, and metastasis. This review summarizes current knowledge regarding GPR68-its expression, regulation, signaling pathways, physiological roles, and functions it regulates in human cancers (including prostate, colon and pancreatic cancer, melanoma, medulloblastoma, and myelodysplastic syndrome)...
January 28, 2019: International Journal of Molecular Sciences
Lu-Yao Guan, Yuan Lu
Ovarian cancer remains the most mortal gynecological cancer in the world. The standard treatment for ovarian cancer remains cytoreductive surgery followed by platinum-based chemotherapy. Although most patients are platinum-sensitive initially, the majority of them will develop platinum resistance after multiple relapses, and platinum-resistant patients have a low response to the second-line chemotherapy. Besides, ovarian cancer is considered to be a highly heterogeneous disease at the molecular level. Molecular targeted therapy is expected to be a more effective and less toxic therapeutic strategy for ovarian cancer...
November 2018: Discovery Medicine
Angiolo Gadducci, Valentina Guarneri, Fedro Alessandro Peccatori, Graziana Ronzino, Giuseppa Scandurra, Claudio Zamagni, Paolo Zola, Vanda Salutari
Epithelial ovarian cancer is the most lethal gynecologic malignancy. In most women, it is diagnosed at an advanced stage, which largely explains the poor prognosis of this malignancy. Germline mutations of the genes BRCA1 and BRCA2, which encode proteins essential for the repair of double-strand DNA breaks through homologous recombination, lead to increased cancer predisposition. BRCA mutations are present in approximately 14% of epithelial ovarian cancers. Somatic BRCA mutations have also been described. Current first-line treatment of high-grade epithelial ovarian cancer includes debulking surgery followed by combination chemotherapy, usually carboplatin and paclitaxel...
January 28, 2019: Journal of Ovarian Research
Rebecca Ann Previs, Angeles Alvarez Secord
Ovarian cancer treatment continues to evolve. Despite aggressive surgery and chemotherapy, most women will ultimately die from disease. Improvement in disease control are due to the incorporation of molecular targeted agents and the adoption of maintenance therapy. Maintenance therapy has been shown to enhance progression-free survival. Recent surgical trials have evaluated the role of neoadjuvant chemotherapy versus primary debulking at the time of diagnosis in advanced stage ovarian cancer. The role of lymph node dissection and secondary cytoreductive surgeries have also been evaluated...
March 2019: Obstetrics and Gynecology Clinics of North America
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