دورية أكاديمية
أعرض في EDS

Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer.

التفاصيل البيبلوغرافية
العنوان: Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer.
المؤلفون: Jain A; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Agostini LC; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., McCarthy GA; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Chand SN; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Ramirez A; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Nevler A; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Cozzitorto J; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Schultz CW; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Lowder CY; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Smith KM; Drug Discovery Unit, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom., Waddell ID; Drug Discovery Unit, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom., Raitses-Gurevich M; Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel., Stossel C; Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Gorman YG; Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel., Atias D; Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel., Yeo CJ; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Winter JM; Surgical Oncology, University Hospitals Cleveland Medical Center, Cleveland, Ohio., Olive KP; Department of Medicine and Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York., Golan T; Oncology Institute, Chaim Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Pishvaian MJ; Department of Gastrointestinal Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, Texas., Ogilvie D; Drug Discovery Unit, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom., James DI; Drug Discovery Unit, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom., Jordan AM; Drug Discovery Unit, Cancer Research UK Manchester Institute, The University of Manchester, Manchester, United Kingdom., Brody JR; The Jefferson Pancreas, Biliary and Related Cancer Center, Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania. jonathan.brody@jefferson.edu.; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
المصدر: Cancer research [Cancer Res] 2019 Sep 01; Vol. 79 (17), pp. 4491-4502. Date of Electronic Publication: 2019 Jul 04.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Baltimore, Md. : American Association for Cancer Research
Original Publication: Chicago [etc.]
مواضيع طبية MeSH: Carcinoma, Pancreatic Ductal/*drug therapy , Glycoside Hydrolases/*antagonists & inhibitors , Pancreatic Neoplasms/*drug therapy, Animals ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Cell Line, Tumor ; DNA Damage ; Enzyme Inhibitors/pharmacology ; Female ; Gene Silencing ; Glycoside Hydrolases/genetics ; Humans ; Mice, Nude ; Molecular Targeted Therapy ; Oxaliplatin/pharmacology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Recombinational DNA Repair ; Small Molecule Libraries/pharmacology ; Xenograft Model Antitumor Assays
مستخلص: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have an average survival of less than 1 year, underscoring the importance of evaluating novel targets with matched targeted agents. We recently identified that poly (ADP) ribose glycohydrolase (PARG) is a strong candidate target due to its dependence on the pro-oncogenic mRNA stability factor HuR ( ELAVL1 ). Here, we evaluated PARG as a target in PDAC models using both genetic silencing of PARG and established small-molecule PARG inhibitors (PARGi), PDDX-01/04. Homologous repair-deficient cells compared with homologous repair-proficient cells were more sensitive to PARGi in vitro . In vivo , silencing of PARG significantly decreased tumor growth. PARGi synergized with DNA-damaging agents (i.e., oxaliplatin and 5-fluorouracil), but not with PARPi therapy. Mechanistically, combined PARGi and oxaliplatin treatment led to persistence of detrimental PARylation, increased expression of cleaved caspase-3, and increased γH2AX foci. In summary, these data validate PARG as a relevant target in PDAC and establish current therapies that synergize with PARGi. SIGNIFICANCE: PARG is a potential target in pancreatic cancer as a single-agent anticancer therapy or in combination with current standard of care.
(©2019 American Association for Cancer Research.)
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معلومات مُعتمدة: C480/A11411 United Kingdom CRUK_ Cancer Research UK; C5759/A17098 United Kingdom CRUK_ Cancer Research UK; R01 CA212600 United States CA NCI NIH HHS; R37 CA227865 United States CA NCI NIH HHS; 17098 United Kingdom CRUK_ Cancer Research UK; P30 CA056036 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Enzyme Inhibitors)
0 (Small Molecule Libraries)
04ZR38536J (Oxaliplatin)
EC 3.2.1.- (Glycoside Hydrolases)
EC 3.2.1.143 (poly ADP-ribose glycohydrolase)
تواريخ الأحداث: Date Created: 20190706 Date Completed: 20200615 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC6816506
DOI: 10.1158/0008-5472.CAN-18-3645
PMID: 31273064
قاعدة البيانات: MEDLINE
الوصف
تدمد:1538-7445
DOI:10.1158/0008-5472.CAN-18-3645