PO.ET06.02 · 实验与分子治疗
DNA Damage and Repair 1
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230 · PDF AZD4956,一种强效且选择性的DNA聚合酶theta抑制剂,在HRR缺陷细胞背景中增强DNA损伤剂的活性并改善新一代PARP1选择性抑制剂saruparib的疗效 AZD4956, a potent and selective inhibitor of DNA polymerase theta, enhances the activity of DNA-damaging agents in HRR defective cellular backgrounds and improves efficacy of the new generation PARP1-selective inhibitor, saruparib Josep V. Forment, Lee Mulderrig, Christelle de Renty, Harriet Southgate, Gemma Jones, Martina Gesu, Rebecca Sargeant, Daniel Sutton, Lenka Oplustil O'Connor, Susan Critchlow, Sabina Cosulich
- 231 231 聚合酶iota驱动BRCA2缺陷型人乳腺上皮细胞中异常的有丝分裂DNA合成与复制应激 Polymerase iota drives aberrant mitotic DNA synthesis and replication stress in BRCA2 deficient human mammary epithelial cells Kavya Vipparthi, Ariana Bellare, Resul Ozbilgic, Mihriban Karaayvaz
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232 · PDF IDE034,一种共同靶向PTK7和B7-H3的双特异性抗体偶联药物,表现出亲合力驱动的选择性以及优于单特异性ADC的增强抗肿瘤活性 IDE034, A bispecific antibody-drug conjugate co-targeting PTK7 and B7-H3, exhibits avidity-driven selectivity and enhanced antitumor activity versus mono-specific ADCs Diana M Munoz Delgado, Ying Zhu, Yanan Guo, Yuelei Shen, Peiran Li, Reeja Maskey, Pei Xin Lim, Megan Conway, Marcus M. Fischer, Vidhya Nagarajan, Arjun A. Rao, Christian Frey, Yuchen Bai, Paul A. Barsanti, Claire Neilan, Mike A. White
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233 · PDF EIK1005的临床前开发,一种强效且选择性的Werner解旋酶抑制剂 Preclinical development of EIK1005, a potent and selective inhibitor of Werner helicase Fernando Rodriguez Perez, Danny Murnock, Juanita Ezemba, Tamer Ahmed, Jose Ortega, Huntly M. Morrison, Rafael Miranda, Taylor Heuer, Stephen Jones, Brenda Smith, Ali Tabatabaei, Stephen Basham, Melissa Dumble, Marcus P. Kelly
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234 · PDF BSM-1516对FEN1抑制的蛋白质组学分析揭示了用于临床前药效学评估的染色质相关生物标志物 Proteomic profiling of FEN1 inhibition by BSM-1516 reveals chromatin-associated biomarkers for preclinical pharmacodynamic evaluation Jason Munguia, Sanjay Agarwalla, Dave Martin, Junhua Fan, Jack Schultz, Celeste Giansanti, David Cortez, David Puerta, Zachary Zimmerman, Konstantin Taganov
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235 · PDF 共价与非共价WRN抑制剂的细胞学比较揭示了共有及独特的应答生物标志物 Cellular comparison of a covalent and non-covalent WRN inhibitor reveals shared and unique response biomarkers Gerarda van de Kamp, Daphne J. F. Kluitmans, Tsang W. Lam, Jeroen A. D. M. de Roos, Janneke J. T. M. Melis, Jeffrey J. Kooijman, Jorg C. J. Benningshof
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236 · PDF 靶向DNA损伤感受器(DDS)以增强EGFR驱动型癌症中Osimertinib的应答 Targeting DNA damage sensors (DDS) to enhance Osimertinib response in EGFR-driven cancers Pamela L. Mendoza-Munoz, Madison E. Gerbig, John J. Turchi, Shadia I. Jalal
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237 · PDF 碱基切除修复抑制剂TRC102在DNA损伤应答过度激活的胶质母细胞瘤中的选择性细胞毒性 Selective Cytotoxicity of Base Excision Repair Inhibitor, TRC102, in DNA Damage Response Hyperactivated Glioblastoma Shaunak Sathe, Qi Li, Jinkyu Jung, Peng Lu, Zach Sergi, Herui Wang, Jing Wu
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238 · PDF 通过基于双链DNA的PROTAC靶向降解DNA连接酶IV以实现精准放疗增敏 Targeted degradation of DNA ligase IV through a double-stranded DNA-based PROTAC for precision radiosensitization Monica Pandey, Daniel S Higginson
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239 · PDF CHK1/2抑制剂ACR-368与ADC载药拓扑异构酶I抑制剂之间的强效协同作用:ADC+ACR-368联合治疗的理论依据 Potent synergy between CHK1/2 inhibitor ACR-368 and the ADC payload topoisomerase I inhibitor: Rationale for ADC + ACR-368 combination therapy Portia Lombardo, Ahmed Youssef, Mohamed Eldeeb, Nina Lipjankic, Martina Pasetto, Ruban Cornelius, Sofija Skoric, Ignacio Arribas Diez, Zachary Best, Anna-Maria Alves, Subodh Kumar, Kate Rappard, Calvin Yang, Corey Xu, Emma Ahrman, Valentina Siino, Taronish Dubash, Joelle Baddour-Sousounis, Reina Improgo, Magnus E. Jakobsson, Ayesha Murshid, Helén Åsa Nilsson, Lei Shi, Caroline Maria Wigerup, Michail Shipitsin, Joon Jung, David Proia, Erick Gamelin, Mansoor Mirza, Kristina Masson, Peter Blume-Jensen
- 240 240 通过腺嘌呤碱基编辑对胰腺导管腺癌进行等位基因特异性的PARP抑制增敏 Allele-specific sensitization of pancreatic ductal adenocarcinoma to PARP inhibition via adenine base editing Jin Zhang, Jingrui Yan, Tianxing Zhou, Xiuchao Wang, Chao Yang, Jun Yu, Jihui Hao
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241 · PDF 靶向药物筛选鉴定出能够加速错配修复缺陷(MMRd)以增强免疫治疗敏感性的新型化合物 Targeted drug screening identifies novel compounds enabling accelerated mismatch repair deficiency (MMRd) for immunotherapy sensitization Benoit Rousseau, Miteshkumar Patel, Karthik Rangavajhula, Lin Zhang, David Mieles, James R. White, Oliver Artz, Shrey Patel, Somer Abdelfattah, Neil Segal, Luis A. Diaz
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242 · PDF 靶向DNA损伤应答传感器复制蛋白A用于首创癌症疗法 Targeting the DNA damage response sensor replication protein A for first in class cancer therapy Pamela VanderVere-Carozza, Matthew R. Jordan, Katherine Pawelczak, John J. Turchi
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243 · PDF 基于DNA纤维的复制表型可区分接受阿泽司替(azenosertib)治疗的高级别子宫内膜癌患者来源类器官(PDO)中的WEE1抑制剂反应 DNA fiber-based replication phenotypes distinguish WEE1-inhibitor response in high-grade endometrial cancer patient-derived organoids (PDOs) treated with azenosertib Elena Ivanova, Ke Cong, Shrabasti Roychoudhury, David Han, Magdalena Zielinska, Minh Ha, Abrielle Jens, Vaishnavi Anand, Bose S. Kochupurakkal, Courtney H. Qi, Arunika Shee, Maureen Mulready, Madison Zizzo, Alexis Rabbitt, Jennifer D. Curtis, Nabihah Tayob, Marisa R. Nucci, Cam A. Tran, Panagiotis A. Konstantinopoulos, Geoffrey I. Shapiro, Dipanjan Chowdhury, Cloud P. Paweletz, Ursula Matulonis, Joyce Liu
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244 · PDF DHX9抑制与同源重组缺陷及dMMR/MSI-H癌症具有合成致死性,并与PARP1抑制和化疗协同 DHX9 inhibition is synthetically lethal with homologous recombination deficient and dMMR/MSI-H cancers and synergizes with PARP1 inhibition and chemotherapy Samantha S. Hodge, Natalie Hill, Jhansi L. Leslie, Umida Djakbrova, Logan Chinn, Saranya Chandrasekar, Susan Paprcka, Ester Fernández-Salas
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245 · PDF 通过联合给予PARG抑制剂扩大PARP抑制剂的治疗窗 Expanding the therapeutic window of PARP inhibitors by co-administering PARG inhibitors Giacomo G. Rossetti, Michalis Petropoulos, Theodoros Rampias, Thanos D. Halazonetis
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246 · PDF 首个口服生物可利用FEN1抑制剂的发现及机制表征,用于治疗HRD和EWS癌症并与多种DDR抑制剂联用 Discovery and mechanistic characterisation of the first oral bioavailable FEN1 inhibitor for treatment of HRD and EWS cancers and combination with various DDR inhibitors Lars T. Burgdorf, Julien Lefranc, Lucy Armstrong, Roch Boivin, Joerg Bomke, Xiaoling Chen, Paula Costales, Owen A. Davis, Lizbeth DeSelm, Elias Elinati, Maria Filipa Pinto, Bruce Follows, Alessandro Galbiati, Catherine Jorand-Lebrun, Timothea Konstantinou, Julian Kreis, Claudio A. Lademann, Birgitta Leuthner, Jayesh B. Majithiya, Balca R. Mardin, Bethany Mason, Claire L. McWhirter, Djordje Musil, Ulrich Pehl, David Perera, Silvia Peripolli, Carl Petersson, Eeson Rajendra, Christin Rakers, Ada Sala-Hojman, Graeme C. M. Smith, Fiona Sorrell, Ana Toste Rêgo, Helen M. R. Robinson, Frank T. Zenke, Robert A. Heald, Sam E. Mann
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247 · PDF ATR 和 Aurora 激酶抑制剂在多种 TNBC 模型中的多组学与临床前评估 Multiomic and preclinical assessment of ATR and Aurora kinase inhibitors in diverse TNBC models Nathan M. Merrill, Hamadi Madhi, Nathalie M. Vandecan, Athena Marie Apfel, Habib Serhan, Peter J. Ulintz, Liwei Bao, Aki Morikawa, Matthew B. Soellner, Soffia D. Merajver
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248 · PDF Nesuparib(JPI-547)作为一种 tankyrase/PARP 双重抑制剂,通过调节 Wnt 和 Hippo 信号通路在小细胞肺癌模型中展现出强效抗肿瘤活性 Nesuparib (JPI-547), a dual tankyrase/PARP inhibitor, exhibits potent antitumor activity in small-cell lung cancer models by modulating Wnt and Hippo signaling pathways Jun Kim, Joon-Hyung Lee, John Kim, Hyunju Cha, Seounghun Kang
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249 · PDF MOMA-313 作为一种 DNA 聚合酶 theta 解旋酶结构域抑制剂,在临床前模型中可阻止 BRCA 回复突变 MOMA-313, an inhibitor of the DNA polymerase theta helicase domain, prevents BRCA reversions in preclinical models Giulia Bottoni, Anthony Tubbs, Kelly McGlynn, Vinny Motwani, Michael Reutershan, Timothy Guzi, Erica Evans, Peter Hammerman, Jordan A. Krall
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250 · PDF 靶向 DNA 损伤修复通路和 CCR2⁺ 髓系细胞以克服小细胞肺癌的放射免疫治疗耐药 Targeting DNA damage repair pathway and CCR2⁺ myeloid cell to overcome radioimmunotherapy resistance in small cell lung cancer Zhuoran Yao, Hui Wang, Kai Kang, Min Yu, Feifei Na, Ren Luo, Linglu Yi, Ruizhan Tong, Jianxin Xue, You Lu
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251 · PDF 靶向 cyclin K-CDK12 通过限制 RPA 染色质加载与三阴性乳腺癌中的 ATR 抑制产生协同作用 Targeting cyclin K-CDK12 synergizes with ATR inhibition by limiting RPA chromatin loading in triple-negative breast cancer Eun-Bee Choi, Sophia Podeszwa, Ah-Ram Kim, Ashwani Bahl, Geoffrey I. Shapiro
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252 · PDF 靶向复制应激促进脊索瘤中的免疫原性细胞死亡 Targeting replication stress promotes immunogenic cell death in chordoma Nindo Punturi, Arijit Ghosh, Caitlin King, Wendy Leung, Joan B. Levy, Lee Zou, Gregory M. Cote, Dan Freed
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253 · PDF PARP 抑制剂联合 Temozolomide 在延胡索酸水合酶缺陷型 RCC 中的抗肿瘤活性 Antitumor activity of PARP inhibitors in combination with Temozolomide in fumarate hydratase-deficient RCC Sameer Issaq, Kylie Enten, Emily Hnath, Komal Rawal, Ramaprasad Srinivasan
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254 · PDF PARP1 选择性抑制剂和捕获剂 saruparib 在体外、体内及临床中实现延长的 PARP1 靶点结合 The PARP1-selective inhibitor and trapper saruparib achieves extended PARP1 target engagement in vitro , in vivo and in the clinic Mark Robert Albertella, Giuditta Illuzzi, Anna D. Staniszewska, Domenic Pilger, Sophie Cooke, Spiros Linardopoulos, Anna Beckett, Christopher Stubbs, Ganesh Moorthy, Mark J. O'Connor