Advances in the treatment of ovarian cancer using PARP inhibitors and the underlying mechanism of resistance.

This study aims to summarize the indications and toxicity of PARP inhibitors, the mechanism of action, targeted treatment of drug resistance, and potential methods to manage drug-resistant diseases. We used the term "ovarian cancer" and the names of each PARP inhibitor as keywords to search articles published in the Medical Subject Headings (MeSH) on Pubmed, along with the keywords "clinicaltrials.gov" and "google.com/patents" as well as "uspto.gov." The FDA has approved olaparib, niraparib, and rucaparib for treatment of recurrent epithelial ovarian cancer (EOC). Talazoparib and veliparib are currently in early trials and show promising clinical results. The mechanism underlying resistance to PARP inhibitors and the clinical strategies to overcome them remain unclear. Understanding the mechanism of resistance to PARP inhibitors and their relationship with platinum resistance may help with the development of antiresistance therapies and optimization of the sequence of drug application in future clinical treatment of ovarian cancer. PMID: 31553293 [PubMed - as supplied by publisher]
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research

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Publication date: Available online 20 December 2019Source: Pathology - Research and PracticeAuthor(s): Zhengmao Zhang, Xiaomeng Dou, Hongfang Yang, Ling Jia, Kaiyun Qin, Xingshuang Gao, Botao Yang, Wenzhe Zhang, Congying Qin, Fenghua Zhang, Baoen ShanAbstractObjectiveTo evaluate the correlation between expression of p53, Livin, Excision repair cross-complementation group 1 (ERCC1), BRCA1 and Poly (ADP-ribose) polymerase 1 (PARP 1) in epithelial ovarian cancer (EOC) tissues with platinum-based chemotherapy and prognosis in patients who received either comprehensive surgical staging or cytoreductive surgery.MethodsThe protei...
Source: Pathology Research and Practice - Category: Pathology Source Type: research
nto Yu Yu Ovarian cancers remain one of the most common causes of gynecologic cancer-related death in women worldwide. The standard treatment comprises platinum-based chemotherapy, and most tumors develop resistance to therapeutic drugs. One mechanism of developing drug resistance is alterations of molecules involved in apoptosis, ultimately assisting in the cells’ capability to evade death. Thus, there is a need to focus on identifying potential drugs that restore apoptosis in cancer cells. Here, we discuss the major inducers of apoptosis mediated through various mechanisms and their usefulness as potentia...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of p...
Source: Clinical Epigenetics - Category: Research Authors: Tags: Research Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion: These findings characterize a novel role of ERα in mediating the molecular connection between hormone and HRR in EOC and encourage hormone replacement therapy for EOC patients.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, Lactobacillus plantarum (L. plantarum) KLDS1.0318 preserved in our laboratory was orally administered to CTX-treated mice to explore its potential effects to attenuate the toxic effects of CTX-induced by modulating intestinal immune response, promoting intestinal integrity and improving metabolic profile. BALB/c mice were randomly divided into six groups including normal control group (NC; non-CTX with sterile saline), model control group (MC; CTX-treated with sterile saline), CTX-treated with L. plantarum KLDS1.0318 (10 mL/kg) groups with three different doses (KLDS1.0318-L, 5 × 107 CFU/mL; KLDS1.0318...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Joe Abdo1, Christopher S. Wichman2, Nicholas E. Dietz1,3, Pawel Ciborowski4, John Fleegel1, Sumeet K. Mittal1,5 and Devendra K. Agrawal1* 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States 2Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States 3Department of Pathology, CHI Health Creighton University Medical Center, College of Medicine, Omaha, NE, United States 4Department of Pharmacology, University of Nebraska Medical Center, Omaha, NE, United States 5Norton Thoracic Institute, St....
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, this study demonstrates that WG-391D exhibits strong antitumor activity against ovarian cancer and indicates that the down-regulation of CDC25B by inhibitors could provide a rationale for ovarian cancer therapy. Introduction Ovarian cancer is one of the most common malignances in females. The American Cancer Society estimated that there were 22,240 cases of ovarian cancer, and 14,070 deaths, in the United States in 2018 (1). During its early stages, ovarian cancer can be asymptomatic; hence, ~70% of patients have advanced disease when diagnosed and ultimately develop chemotherapeutic drug resistance an...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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