keyword
MENU ▼
Read by QxMD icon Read
search

Volasertib

keyword
https://www.readbyqxmd.com/read/29535822/the-polo-like-kinase-1-inhibitor-volasertib-synergistically-increases-radiation-efficacy-in-glioma-stem-cells
#1
Jianwen Dong, Soon Young Park, Nghi Nguyen, Ravesanker Ezhilarasan, Emmanuel Martinez-Ledesma, Shaofang Wu, Verlene Henry, Yuji Piao, Ningyi Tiao, David Brunell, Clifford Stephan, Roel Verhaak, Erik Sulman, Veerakumar Balasubramaniyan, John F de Groot
Background: Despite the availability of hundreds of cancer drugs, there is insufficient data on the efficacy of these drugs on the extremely heterogeneous tumor cell populations of glioblastoma (GBM). Results: The PKIS of 357 compounds was initially evaluated in 15 different GSC lines which then led to a more focused screening of the 21 most highly active compounds in 11 unique GSC lines using HTS screening for cell viability. We further validated the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent and in combination with ionizing radiation (IR)...
February 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29515764/polo-like-kinase-inhibitor-volasertib-marginally-enhances-the-efficacy-of-the-novel-fc-engineered-anti-cd33-antibody-bi-836858-in-acute-myeloid-leukemia
#2
Bhavani Gopalakrishnan, Carolyn Cheney, Rajeswaran Mani, Xiaokui Mo, Donna Bucci, Alison Walker, Rebecca Klisovic, Bhavana Bhatnagar, Katherine Walsh, Bjoern Rueter, Irene C Waizenegger, Karl-Heinz Heider, William Blum, Sumithira Vasu, Natarajan Muthusamy
Acute myeloid leukemia (AML) is the second most common type of leukemia in adults. Incidence of AML increases with age with a peak incidence at 67 years. Patients older than 60 years have an unfavorable prognosis due to resistance to conventional chemotherapy. Volasertib (BI 6727) is a cell-cycle regulator targeting polo-like kinase which has been evaluated in clinical trials in AML. We evaluated effects of volasertib in primary patient samples and NK cells. At equivalent doses, volasertib is cytotoxic to AML blasts but largely spares healthy NK cells...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29476067/bi-2536-and-bi-6727-dual-polo-like-kinase-bromodomain-inhibitors-effectively-reactivate-latent-hiv-1
#3
Jin Gohda, Kazuo Suzuki, Kai Liu, Xialin Xie, Hiroaki Takeuchi, Jun-Ichiro Inoue, Yasushi Kawaguchi, Takaomi Ishida
HIV-1 latent reservoirs harbouring silenced but replication-competent proviruses are a major obstacle against viral eradication in infected patients. The "shock and kill" strategy aims to reactivate latent provirus with latency reversing agents (LRAs) in the presence of antiretroviral drugs, necessitating the development of effective and efficient LRAs. We screened a chemical library for potential LRAs and identified two dual Polo-like kinase (PLK)/bromodomain inhibitors, BI-2536 and BI-6727 (volasertib), which are currently undergoing clinical trials against various cancers...
February 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29454094/synergistic-activity-of-bet-inhibitor-bi-894999-with-plk-inhibitor-volasertib-in-aml-in-vitro-and-in-vivo
#4
Ulrike Tontsch-Grunt, Dorothea Rudolph, Irene Waizenegger, Anke Baum, Daniel Gerlach, Harald Engelhardt, Melanie Wurm, Fabio Savarese, Norbert Schweifer, Norbert Kraut
Interactions between a new potent Bromodomain and extraterminal domain (BET) inhibitor BI 894999 and the polo-like kinase (PLK) inhibitor volasertib were studied in acute myeloid leukemia cell lines in vitro and in vivo. We provide data for the distinct mechanisms of action of these two compounds with a potential utility in AML based on gene expression, cell cycle profile and modulation of PD biomarkers such as MYC and HEXIM1. In contrast to BI 894999, volasertib treatment neither affects MYC nor HEXIM1 expression, but augments and prolongs the decrease of MYC expression caused by BI 894999 treatment...
May 1, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29391599/targeting-plk1-overcomes-t-dm1-resistance-via-cdk1-dependent-phosphorylation-and-inactivation-of-bcl-2-xl-in-her2-positive-breast-cancer
#5
Özge Saatci, Simone Borgoni, Özge Akbulut, Selvi Durmuş, Umar Raza, Erol Eyüpoğlu, Can Alkan, Aytekin Akyol, Özgür Kütük, Stefan Wiemann, Özgür Şahin
Trastuzumab-refractory, HER2 (human epidermal growth factor receptor 2)-positive breast cancer is commonly treated with trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the microtubule-targeting agent, DM1. However, drug response reduces greatly over time due to acquisition of resistance whose molecular mechanisms are mostly unknown. Here, we uncovered a novel mechanism of resistance against T-DM1 by combining whole transcriptome sequencing (RNA-Seq), proteomics and a targeted small interfering RNA (siRNA) sensitization screen for molecular level analysis of acquired and de novo T-DM1-resistant models of HER2-overexpressing breast cancer...
April 2018: Oncogene
https://www.readbyqxmd.com/read/29383095/polo-like-kinase-1-plk-1-and-c-myc-inhibition-with-the-dual-kinase-bromodomain-inhibitor-volasertib-in-aggressive-lymphomas
#6
Carlos Murga-Zamalloa, Avery Polk, Walter Hanel, Pinki Chowdhury, Noah Brown, Alexandra C Hristov, Nathanael G Bailey, Tianjiao Wang, Tycel Phillips, Sumana Devata, Pradeep Poonnen, Juan Gomez-Gelvez, Kedar V Inamdar, Ryan A Wilcox
Survival following anthracycline-based chemotherapy remains poor among patients with most T-cell lymphoproliferative disorders. This may be attributed, at least in part, to cell-autonomous mechanisms of chemotherapy resistance observed in these lymphomas, including the loss of important tumor suppressors and the activation of signaling cascades that culminate in the expression and activation of transcription factors promoting cell growth and survival. Therefore, the identification of novel therapeutic targets is needed...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228610/targeting-polo-like-kinase-1-in-smarcb1-deleted-atypical-teratoid-rhabdoid-tumor
#7
Irina Alimova, Angela M Pierce, Peter Harris, Andrew Donson, Diane K Birks, Eric Prince, Ilango Balakrishnan, Nicholas K Foreman, Marcel Kool, Lindsey Hoffman, Sujatha Venkataraman, Rajeev Vibhakar
Atypical teratoid rhabdoid tumor (ATRT) is an aggressive and malignant pediatric brain tumor. Polo-like kinase 1 ( PLK1 ) is highly expressed in many cancers and essential for mitosis. Overexpression of PLK1 promotes chromosome instability and aneuploidy by overriding the G2-M DNA damage and spindle checkpoints. Recent studies suggest that targeting PLK1 by small molecule inhibitors is a promising approach to tumor therapy. We investigated the effect of PLK1 inhibition in ATRT. Gene expression analysis showed that PLK1 was overexpressed in ATRT patient samples and tumor cell lines...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29186071/volasertib-enhances-sensitivity-to-trail-in-renal-carcinoma-caki-cells-through-downregulation-of-c-flip-expression
#8
Mi-Yeon Jeon, Kyoung-Jin Min, Seon Min Woo, Seung Un Seo, Shin Kim, Jong-Wook Park, Taeg Kyu Kwon
Polo-like kinase 1 (PLK1) plays major roles in cell cycle control and DNA damage response. Therefore, PLK1 has been investigated as a target for cancer therapy. Volasertib is the second-in class dihydropteridinone derivate that is a specific PLK1 inhibitor. In this study, we examined that combining PLK1 inhibitor with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) would have an additive and synergistic effect on induction of apoptosis in cancer cells. We found that volasertib alone and TRAIL alone had no effect on apoptosis, but the combined treatment of volasertib and TRAIL markedly induced apoptosis in Caki (renal carcinoma), A498 (renal carcinoma) and A549 (lung carcinoma) cells, but not in normal cells (human skin fibroblast cells and mesangial cells)...
November 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29108241/identification-of-volasertib-resistant-mechanism-and-evaluation-of-combination-effects-with-volasertib-and-other-agents-on-acute-myeloid-leukemia
#9
Yoshiya Adachi, Yuichi Ishikawa, Hitoshi Kiyoi
Volasertib, a selective PLK1 inhibitor, was effective for acute myeloid leukemia (AML) patients in clinical trials. However, its efficacy was limited in mono-therapy, and a higher incidence of fatal events was revealed in the combination with low-dose cytarabine. Thus, optimization of combination therapy with volasertib and other agents is necessary for its clinical development, and the predictive factors for response or resistance to volasertib remain largely unknown. In this study, we investigated the resistance mechanism in volasertib-resistant cell lines and the combination effects with other agents, such as azacitidine (AZA), on AML cells...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29035889/inhibition-of-suicidal-erythrocyte-death-by-volasertib
#10
Abdulla Al Mamun Bhuyan, A K M Ashiqul Haque, Itishri Sahu, Hang Cao, Michael S D Kormann, Florian Lang
BACKGROUND/AIMS: The Polo-like kinase 1 (Plk1) inhibitor volasertib is used in the treatment of malignancy. Volasertib is partially effective by triggering suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter suicidal cell death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage. Stimulators of eryptosis include energy depletion, hyperosmotic shock, oxidative stress and excessive increase of cytosolic Ca2+ activity ([Ca2+]i)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28778089/identification-of-volasertib-resistant-mechanism-and-evaluation-of-combination-effects-with-volasertib-and-other-agents-on-acute-myeloid-leukemia
#11
Yoshiya Adachi, Yuichi Ishikawa, Hitoshi Kiyoi
Volasertib, a selective PLK1 inhibitor, was effective for acute myeloid leukemia (AML) patients in clinical trials. However, its efficacy was limited in mono-therapy, and a higher incidence of fatal events was revealed in the combination with low-dose cytarabine. Thus, optimization of combination therapy with volasertib and other agents is necessary for its clinical development, and the predictive factors for response or resistance to volasertib remain largely unknown. In this study, we investigated the resistance mechanism in volasertib-resistant cell lines and the combination effects with other agents, such as azacitidine (AZA), on AML cells...
July 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652654/bcl-2-degradation-is-an-additional-pro-apoptotic-effect-of-polo-like-kinase-inhibition-in-cholangiocarcinoma-cells
#12
Svenja Sydor, Sami Jafoui, Lena Wingerter, Sandra Swoboda, Joachim C Mertens, Guido Gerken, Ali Canbay, Andreas Paul, Christian D Fingas
AIM: To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment. METHODS: As most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators...
June 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28631179/population-pharmacokinetics-of-volasertib-administered-in-patients-with-acute-myeloid-leukaemia-as-a-single-agent-or-in-combination-with-cytarabine
#13
Belén P Solans, Angèle Fleury, Matthias Freiwald, Holger Fritsch, Karin Haug, Iñaki F Trocóniz
BACKGROUND: Volasertib, a potent and selective polo-like kinase inhibitor, has shown to increase response rates and improve survival with a clinically manageable safety profile, administered alone and in combination with cytarabine in patients with acute myeloid leukaemia. OBJECTIVES: The objectives of this analysis were to describe the pharmacokinetics of volasertib and cytarabine, administered as single agents or in combination. METHODS: Three thousand, six hundred and six plasma volasertib concentrations from 501 patients receiving either volasertib alone, or in combination with cytarabine, and 826 plasma cytarabine concentrations from 650 patients receiving cytarabine as multiple subcutaneous injections per cycle either alone, or in combination with volasertib, were analysed using NONMEM Version 7...
March 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28556483/drug-sensitivity-and-resistance-testing-identifies-plk1-inhibitors-and-gemcitabine-as-potent-drugs-for-malignant-peripheral-nerve-sheath-tumors
#14
Matthias Kolberg, Jarle Bruun, Astrid Murumägi, John P Mpindi, Christian H Bergsland, Maren Høland, Ina A Eilertsen, Stine A Danielsen, Olli Kallioniemi, Ragnhild A Lothe
Patients with malignant peripheral nerve sheath tumor (MPNST), a rare soft tissue cancer associated with loss of the tumor suppressor neurofibromin (NF1), have poor prognosis and typically respond poorly to adjuvant therapy. We evaluated the effect of 299 clinical and investigational compounds on seven MPNST cell lines, two primary cultures of human Schwann cells, and five normal bone marrow aspirates, to identify potent drugs for MPNST treatment with few side effects. Top hits included Polo-like kinase 1 (PLK1) inhibitors (volasertib and BI2536) and the fluoronucleoside gemcitabine, which were validated in orthogonal assays measuring viability, cytotoxicity, and apoptosis...
September 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28482026/preclinical-drug-screen-reveals-topotecan-actinomycin-d-and-volasertib-as-potential-new-therapeutic-candidates-for-etmr-brain-tumor-patients
#15
Christin Schmidt, Nil A Schubert, Sebastian Brabetz, Norman Mack, Benjamin Schwalm, Jennifer A Chan, Florian Selt, Christel Herold-Mende, Olaf Witt, Till Milde, Stefan M Pfister, Andrey Korshunov, Marcel Kool
Background: Embryonal tumor with multilayered rosettes (ETMR) is a rare and aggressive embryonal brain tumor that solely occurs in infants and young children and has only recently been recognized as a separate brain tumor entity in the World Health Organization classification for CNS tumors. Patients have a very dismal prognosis with a median survival of 12 months upon diagnosis despite aggressive treatment. The aim of this study was to develop novel treatment regimens in a preclinical drug screen in order to inform potentially more active clinical trial protocols...
November 29, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28420416/emerging-therapies-for-acute-myeloid-leukemia
#16
REVIEW
Caner Saygin, Hetty E Carraway
Acute myeloid leukemia (AML) is characterized by clinical and biological heterogeneity. Despite the advances in our understanding of its pathobiology, the chemotherapy-directed management has remained largely unchanged in the past 40 years. However, various novel agents have demonstrated clinical activity, either as single agents (e.g., isocitrate dehydrogenase (IDH) inhibitors, vadastuximab) or in combination with standard induction/consolidation at diagnosis and with salvage regimens at relapse. The classes of agents described in this review include novel cytotoxic chemotherapies (CPX-351 and vosaroxin), epigenetic modifiers (guadecitabine, IDH inhibitors, histone deacetylase (HDAC) inhibitors, bromodomain and extraterminal (BET) inhibitors), FMS-like tyrosine kinase receptor 3 (FLT3) inhibitors, and antibody-drug conjugates (vadastuximab), as well as cell cycle inhibitors (volasertib), B-cell lymphoma 2 (BCL-2) inhibitors, and aminopeptidase inhibitors...
April 18, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28416758/synergistic-interactions-between-plk1-and-hdac-inhibitors-in-non-hodgkin-s-lymphoma-cells-occur-in-vitro-and-in-vivo-and-proceed-through-multiple-mechanisms
#17
Tri Nguyen, Rebecca Parker, Elisa Hawkins, Beata Holkova, Victor Yazbeck, Akhil Kolluri, Maciej Kmieciak, Mohamed Rahmani, Steven Grant
Interactions between the polo-like kinase 1 (PLK1) inhibitor volasertib and the histone deacetylase inhibitor (HDACI) belinostat were examined in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) cells in vitro and in vivo. Exposure of DLBCL cells to very low concentrations of volasertib in combination with belinostat synergistically increased cell death (apoptosis). Similar interactions occurred in GC-, ABC-, double-hit DLBCL cells, MCL cells, bortezomib-resistant cells and primary lymphoma cells...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416751/proteasome-inhibition-enhances-the-efficacy-of-volasertib-induced-mitotic-arrest-in-aml-in-vitro-and-prolongs-survival-in-vivo
#18
Dominik Schnerch, Julia Schüler, Marie Follo, Julia Felthaus, Dagmar Wider, Kathrin Klingner, Christine Greil, Justus Duyster, Monika Engelhardt, Ralph Wäsch
Elderly and frail patients, diagnosed with acute myeloid leukemia (AML) and ineligible to undergo intensive treatment, have a dismal prognosis. The small molecule inhibitor volasertib induces a mitotic block via inhibition of polo-like kinase 1 and has shown remarkable anti-leukemic activity when combined with low-dose cytarabine. We have demonstrated that AML cells are highly vulnerable to cell death in mitosis yet manage to escape a mitotic block through mitotic slippage by sustained proteasome-dependent slow degradation of cyclin B...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28061448/targeting-basal-like-breast-tumors-with-bromodomain-and-extraterminal-domain-bet-and-polo-like-kinase-inhibitors
#19
Cristina Nieto-Jiménez, Ana Alcaraz-Sanabria, Javier Pérez-Peña, Verónica Corrales-Sánchez, Gemma Serrano-Heras, Eva M Galán-Moya, Leticia Serrano-Oviedo, Juan Carlos Montero, Miguel Burgos, Juan Llopis, Atanasio Pandiella, Alberto Ocaña
Metastatic triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options, and no targeted therapies available. Triple negative tumors and the basal-like genomic subtype, are both characterized by a high proliferation rate and an increase in cell division. In this context, protein kinases involved in the mitotic formation have a relevant role in this tumor subtype. Recently, Bromodomain and extraterminal domain (BET) inhibitors have shown to be active in this disease by modulating the expression of several transcription factors...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/27904765/volasertib-suppresses-the-growth-of-human-hepatocellular-carcinoma-in-vitro-and-in-vivo
#20
Di-Wei Zheng, You-Qiu Xue, Yong Li, Jin-Ming Di, Jian-Ge Qiu, Wen-Ji Zhang, Qi-Wei Jiang, Yang Yang, Yao Chen, Meng-Ning Wei, Jia-Rong Huang, Kun Wang, Xing Wei, Zhi Shi
Hepatocellular carcinoma (HCC) is the sixth most frequent malignant tumor with poor prognosis, and its clinical therapeutic outcome is poor. Volasertib, a potent small molecular inhibitor of polo-like kinase 1 (PLK1), is currently tested for treatment of multiple cancers in the clinical trials. However, the antitumor effect of volasertib on HCC is still unknown. In this study, our data show that volasertib is able to induce cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the spindle abnormalities in human HCC cells...
2016: American Journal of Cancer Research
keyword
keyword
6847
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"