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Ovarian cancer target drugs

Zalitha Pieterse, Monica Angelica Amaya-Padilla, Terence Singomat, Mudra Binju, Bau Dilam Madjid, Yu Yu, Pritinder Kaur
Ovarian cancer is typically diagnosed at advanced stages (III or IV), with metastasis ensuing at stage III. Complete remission is infrequent and is not achieved in almost half of the women diagnosed with ovarian cancer. Consequently, management and treatment of this disease is challenging as many patients are faced with tumour recurrence disseminating to surrounding organs further complicated with acquired chemo-resistance. The cancer stem cell theory proposes the idea that a drug resistant subset of tumour cells drive tumour progression, metastasis and ultimately, recurrent disease...
November 30, 2018: International Journal of Biochemistry & Cell Biology
Masahiro Yamamoto, Shuhei Suzuki, Keita Togashi, Tomomi Sanomachi, Shizuka Seino, Chifumi Kitanaka, Masashi Okada
BACKGROUND: AS602801, a novel inhibitor of c-Jun N-terminal kinase (JNK), suppresses tumor initiation capacity and metastatic potential of cancer stem cells (CSCs). However, it remains unknown whether this inhibitor can chemosensitize CSCs. MATERIALS AND METHODS: Using A2780 CSLC, a CSC line derived from ovarian cancer, this study examined the combinational effects of AS602801 and carboplatin or paclitaxel and explored the mechanism of those effects. RESULTS: AS602801 chemosensitized A2780 CSLC cells to carboplatin and paclitaxel...
December 2018: Anticancer Research
Faye R Harris, Piyan Zhang, Lin Yang, Xiaonan Hou, Konstantinos Leventakos, Saravut J Weroha, George Vasmatzis, Irina V Kovtun
Ovarian cancer is most lethal gynecologic malignancy. About 75% of ovarian cancer patients relapse and/or develop chemo-resistant disease after initial response to standard-of-care treatment with platinum-based therapies. HER2 amplifications and overexpression in ovarian cancer are reported to vary, and responses to HER2 inhibitors have been poor. Next generation sequencing technologies in conjunction with testing using patient-derived xenografts (PDX) allow validation of personalized treatments. Using a whole-genome mate-pair next generation sequencing (MPseq) protocol, we identified several high grade serous ovarian cancers (HGS-OC) with DNA alterations in genes encoding members of the ERBB2 pathway...
November 30, 2018: Molecular Oncology
Imran Rizvi, Shubhankar Nath, Girgis Obaid, Mustafa Kemal Ruhi, Kaitlin Moore, Shazia Bano, David Kessel, Tayyaba Hasan
A major objective in developing new treatment approaches for lethal tumors is to reduce toxicity to normal tissues while maintaining therapeutic efficacy. Photodynamic therapy (PDT) provides a mechanistically-distinct approach to treat tumors without the systemic toxicity of chemotherapy drugs. PDT involves the light-based activation of a small molecule, a photosensitizer (PS), to generate reactive molecular species (RMS) that are toxic to target tissue. Depending on the PS localization, various cellular and subcellular components can be targeted, causing selective photodamage...
November 29, 2018: Photochemistry and Photobiology
Erfaneh Ghassami, Jaleh Varshosaz, Mohsen Minaiyan, Mehrab Nasirikenari, Seyed Mohammad Hoseini
BACKGROUND: Docetaxel is a notably efficient anticancer drug administered for several types of malignancies including ovarian cancer. However, various side effects caused either by nonspecific distribution of the active ingredient or by high contents of Tween 80 and ethanol in the currently marketed formulations, could even deprive the patients of the treatment. OBJECTIVES: In the current study, a novel targeted delivery system composed of Ecoflex® polymeric nanoparticles loaded with docetaxel and equipped with HER-2 specific aptemer molecules were evaluated regarding blood and tissue toxicity, and biodistribution...
November 28, 2018: Recent Patents on Nanotechnology
Pinar Kanlikilicer, Recep Bayraktar, Merve Denizli, Mohammed H Rashed, Cristina Ivan, Burcu Aslan, Rahul Mitra, Kubra Karagoz, Emine Bayraktar, Xinna Zhang, Cristian Rodriguez-Aguayo, Amr Ahmed El-Arabey, Nermin Kahraman, Seyda Baydogan, Ozgur Ozkayar, Michael L Gatza, Bulent Ozpolat, George A Calin, Anil K Sood, Gabriel Lopez-Berestein
BACKGROUND: Circulating miRNAs are known to play important roles in intercellular communication. However, the effects of exosomal miRNAs on cells are not fully understood. METHODS: To investigate the role of exosomal miR-1246 in ovarian cancer (OC) microenvironment, we performed RPPA as well as many other in vitro functional assays in ovarian cancer cells (sensitive; HeyA8, Skov3ip1, A2780 and chemoresistant; HeyA8-MDR, Skov3-TR, A2780-CP20). Therapeutic effect of miR-1246 inhibitor treatment was tested in OC animal model...
November 25, 2018: EBioMedicine
Jeanne M Quinn, Molly M Greenwade, Marguerite L Palisoul, Gregory Opara, Katina Massad, Lei Guo, Peinan Zhao, Hollie Beck-Noia, Ian S Hagemann, Andrea R Hagemann, Carolyn K McCourt, Premal H Thaker, Matthew A Powell, David G Mutch, Katherine C Fuh
Ovarian cancer (OvCa), one of the deadliest malignancies in female cancer patients, is characterized by recurrence and poor response to cytotoxic chemotherapies. Fewer than 30% of patients with resistant disease will respond to additional chemotherapy treatments. This study aims to determine whether and how inhibition of the receptor tyrosine kinase AXL can restore sensitivity to front-line platinum and taxane therapy in OvCa. AXL staining was quantified in a patient tissue microarray and correlated with chemoresponse of patients...
November 26, 2018: Molecular Cancer Therapeutics
Lara Sánchez-Barroso, Maria Apellaniz-Ruiz, Gerardo Gutiérrez-Gutiérrez, María Santos, Juan M Roldán-Romero, Maria Curras, Laura Remacha, Bruna Calsina, Isabel Calvo, María Sereno, María Merino, Jesús García-Donas, Beatriz Castelo, Eva Guerra, Rocio Letón, Cristina Montero-Conde, Alberto Cascón, Lucía Inglada-Pérez, Mercedes Robledo, Cristina Rodríguez-Antona
BACKGROUND: Peripheral neuropathy is the dose-limiting toxicity of many oncology drugs, including paclitaxel. There is large interindividual variability in the neuropathy, and several risk factors have been proposed; however, many have not been replicated. Here we present a comprehensive study aimed at identifying treatment and physiopathology-related paclitaxel-induced neuropathy risk factors in a large cohort of well-characterized patients. PATIENTS AND METHODS: Analyses included 503 patients with breast or ovarian cancer who received paclitaxel treatment...
November 23, 2018: Oncologist
Stuart R Pierce, Leslie H Clark
Importance: Ovarian, fallopian tube, and primary peritoneal cancers constitute the deadliest gynecologic malignancies. After primary cytoreductive surgery, there are several standard first-line cytotoxic treatments for providers to consider. Newer molecular targeted therapies are becoming more common and may have a role as first-line therapy in the future. Objective: This article provides an evidence-based review of all approved standard therapies for first-line treatment of advanced-stage, high-grade serous ovarian cancer...
November 2018: Obstetrical & Gynecological Survey
Sarah Nersesian, Rodette Williams, Daniel Newsted, Kavan Shah, Stephanie Young, P Andrew Evans, John S Allingham, Andrew W Craig
Amplification of HER2 leads to development of HER2-positive (HER2+) cancers with high rates of metastasis compared to other cancer subtypes. The goal of this study was to probe the vulnerability of HER2+ cancer cells to a filamentous actin (F-actin) severing and capping toxin. The growth and viability of human HER2+ breast cancer (HCC1954) and ovarian cancer (SKOV3) cell lines were significantly impaired upon treatment with the marine macrolide mycalolide B (Myc B) at doses above 100 nanomolar. Further testing of Myc B in combination with the antibody-drug conjugate Trastuzumab-emtansine (T-DM1) led to improved killing of SKOV3 cells compared to either treatment alone...
November 22, 2018: Scientific Reports
Diana C Pearre, Krishnansu S Tewari
The last 2 years have ushered in a new era in ovarian cancer therapy with the US Food and Drug Administration's (FDA) approval of poly-ADP ribose polymerase (PARP) inhibitors (PARPi). One of the deadliest cancers that women experience, ovarian cancer, is most often diagnosed in advanced stages. Although cytoreductive surgery and (platinum/taxane-based) chemotherapy can place the majority of patients into remission, most will experience a relapse of their disease in their lifetime. This has led to studies exploring the benefits and efficacy of maintenance treatment...
2018: Therapeutics and Clinical Risk Management
Meinrad Drexel, Johannes Kirchmair, Sandra Santos-Sierra
INH14 (N-(4-ethylphenyl)-N'-phenylurea) is a fragment-like compound that inhibits the Toll-like receptor 2 (TLR2)-mediated inflammatory activity and also other inflammatory pathways (i.e. TLR4, TNF-R and IL-1R). In this study, we determined the molecular target of INH14. Over-expression of proteins which are part of the TLR2 pathway in cells treated with INH14 indicated that the compound´s target lies downstream of the complex TAK1/TAB1. Immunoblot assays showed that INH14 decreased IkBα degradation in cells activated by lipopeptide (TLR2 ligand)...
November 17, 2018: Chembiochem: a European Journal of Chemical Biology
Z Ping Lin, Yong-Lian Zhu, Ying-Chun Lo, Jake Moscarelli, Amy Xiong, Yasmin Korayem, Pamela H Huang, Smith Giri, Patricia LoRusso, Elena S Ratner
PARP inhibitors target BRCA mutations and defective homologous recombination repair (HRR) for the treatment of epithelial ovarian cancer (EOC). However, the treatment of HRR-proficient EOC with PARP inhibitors remains challenging. The objective of this study was to determine whether the combination of triapine (ribonucleotide reductase inhibitor), cediranib (vascular endothelial growth factor receptor tyrosine kinase inhibitor), and the PARP inhibitor olaparib synergized against BRCA wild-type and HRR-proficient EOC in xenograft mouse models...
2018: PloS One
Ying Jiang, Jing Jiang, Haiqing Jia, Zhiwei Qiao, Jingru Zhang
BACKGROUND/AIMS: In platinum-based chemotherapy for ovarian cancer, acquired drug resistance is a frequent occurrence. Because recent studies have demonstrated that dysregulation of microRNAs (miRNAs) is partly responsible for the induction of acquired drug resistance in cancers, we hypothesized that correcting the dysregulation of key miRNAs would reverse the acquired resistance to platinum-based drugs in ovarian cancer. METHODS: Cisplatin-resistant SKOV3 and A2780 ovarian cancer cell lines (SKOV3-R and A2780-R, respectively) were established by long-term exposure to cisplatin...
2018: Cellular Physiology and Biochemistry
Shou Li, Xiaoyun Zhao, Shijie Chang, Yanqiu Li, Min Guo, Yifu Guan
ERp57 has been identified to be associated with the chemoresistance of human ovarian cancer. However, its biological roles in the chemoresistance phenotype remain unclear. In the present study, the association of ERp57 with paclitaxel‑resistant cellular behavior was investigated and the sensitivity enhancement of chemoresistant human ovarian cancer cells to paclitaxel was examined using ERp57‑small interfering (si)RNA silencing. Cell viability, cell proliferation, cell apoptosis and cell migration were detected using an MTT assay, clonogenic assay, flow cytometry analysis and transwell assay...
January 2019: International Journal of Oncology
Zhi Huang, Wei Zhou, Yongtao Li, Mei Cao, Tianqi Wang, Yakun Ma, Qingxiang Guo, Xin Wang, Chao Zhang, Chenglan Zhang, Wenzhi Shen, Yanhua Liu, Yanan Chen, Jianyu Zheng, Shengyong Yang, Yan Fan, Rong Xiang
Despite initial progress in preclinical models, most known histone deacetylase inhibitors (HDACis) used as a single agent have failed to show clinical benefits in nearly all types of solid tumours. Hence, the efficacy of HDACis in solid tumours remains uncertain. Herein, we developed a hybrid HDAC inhibitor that sensitized solid tumours to HDAC-targeted treatment. Methods: A hybrid molecule, Roxyl-zhc-84 was designed and synthesized with novel architecture. The pharmacokinetics and toxicity of Roxyl-zhc-84 were analysed...
2018: Theranostics
Sabine Schuster, Beáta Biri-Kovács, Bálint Szeder, László Buday, János Gardi, Zsuzsanna Szabó, Gábor Halmos, Gábor Mező
Receptors for gonadotropin releasing hormone (GnRH) are highly expressed in various human cancers including breast, ovarian, endometrial, prostate and colorectal cancer. Ligands like human GnRH-I or the sea lamprey analogue GnRH-III represent a promising approach for the development of efficient drug delivery systems for targeted tumor therapy. Here, we report on the synthesis and cytostatic effect of 14 oxime bond-linked daunorubicin GnRH-III conjugates containing a variety of unnatural amino acids within the peptide sequence...
November 9, 2018: Pharmaceutics
Yusuke Kobayashi, Kouji Banno, Haruko Kunitomi, Shimpei Nagai, Takayuki Takahashi, Mayuka Anko, Moito Iijima, Takashi Takeda, Yusuke Matoba, Kanako Nakamura, Kosuke Tsuji, Eiichiro Tominaga, Daisuke Aoki
Novel pharmacological therapies are in development for cancer, ranging from conventional chemotherapeutic drugs to molecular targeted drugs, antibody-based drugs, and immune checkpoint inhibitors, which are developed using new technologies. However, the increasing cost of new drug development is increasing the costs of national healthcare and putting pressure on government finances worldwide. Under these circumstances, drug repositioning (i.e. discovering novel effects of existing drugs, thereby allowing their use to treat other diseases) has become a major focus because of reliability and cost reduction...
November 8, 2018: European Journal of Cancer Prevention
Eva Villar-Alvarez, Adriana Cambón, Alberto Pardo, Víctor X Mosquera, Alberto Bouzas-Mosquera, Antonio Topete, Silvia Barbosa, Pablo Taboada, Víctor Mosquera
In this work, multifunctional nanocarriers consisting of poly(sodium-4-styrenesulfonate) (PSS)/doxorubicin (DOXO)/poly-l-lysine hydrobromide (PLL)/hyaluronic acid (HA)-coated and (PSS/DOXO/PLL)2 /HA-coated gold nanorods were assembled by the layer-by-layer technique with the aims of coupling the plasmonic photothermal properties of the metal nanoparticles for plasmonic hyperthermia and the chemoaction of drug DOXO for potential intended combinatorial cancer therapeutics in the future as well as providing different strategies for the controlled and sustained release of the cargo drug molecules...
October 31, 2018: ACS Omega
Leilei Niu, Hua Ni, Yingzi Hou, Quan Du, Hua Li
Drug-resistance of platinum remains a big challenge for effective treatment of patients with ovarian cancer. MicroRNAs (miRNAs) act as post-transcriptional regulators of gene expression and are associated with multi-drug resistance. Our study aims on identifying role of miRNAs in drug-resistance of platinum in ovarian cancer. In present study, we compared the expression profiles of miRNAs between three pairs of platinum-resistant and platinum-sensitive ovarian tissues and found that miR-509-3p was significantly down-regulated in cisplatin-resistant ovarian cancer tissues...
November 5, 2018: Gene
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