000839529 000__ 04491cam\a2200493Ii\4500 000839529 001__ 839529 000839529 005__ 20230306144734.0 000839529 006__ m\\\\\o\\d\\\\\\\\ 000839529 007__ cr\un\nnnunnun 000839529 008__ 180531s2018\\\\sz\a\\\\o\\\\\000\0\eng\d 000839529 019__ $$a1038068046 000839529 020__ $$a9783319758367$$q(electronic book) 000839529 020__ $$a3319758365$$q(electronic book) 000839529 020__ $$z9783319758343 000839529 0247_ $$a10.1007/978-3-319-75836-7$$2doi 000839529 035__ $$aSP(OCoLC)on1038067515 000839529 035__ $$aSP(OCoLC)1038067515$$z(OCoLC)1038068046 000839529 040__ $$aGW5XE$$beng$$erda$$epn$$cGW5XE$$dEBLCP$$dN$T$$dUAB$$dOCLCF$$dOCLCQ 000839529 049__ $$aISEA 000839529 050_4 $$aRC270.8 000839529 08204 $$a616.9/9406$$223 000839529 24500 $$aTargeting the DNA damage response for anti-cancer therapy /$$cJohn Pollard, Nicola Curtin, editors. 000839529 264_1 $$aCham, Switzerland :$$bHumana Press,$$c2018. 000839529 300__ $$a1 online resource (ix, 401 pages) :$$billustrations. 000839529 336__ $$atext$$btxt$$2rdacontent 000839529 337__ $$acomputer$$bc$$2rdamedia 000839529 338__ $$aonline resource$$bcr$$2rdacarrier 000839529 4901_ $$aCancer drug discovery and development,$$x2196-9906 000839529 5050_ $$aIntro; Contents; Contributors; Chapter 1: Targeting DNA Repair in Anti-Cancer Treatments; 1.1 PARP Inhibitors to Targeted DNA Repair; 1.2 Limits to the Synthetic Lethal Approach of Targeting Cancer; 1.3 Combining Chemotherapy Treatment with DNA Repair Inhibitors; 1.4 Exploiting the Inherent High Level of DNA Damage in Cancers; Replication Stress; 1.5 Future Challenges in Targeting DNA Repair for Cancer Treatments; References; Chapter 2: The DNA Damage Response: Roles in Cancer Etiology and Treatment; 2.1 Problems Associated with Current Chemo- and Radiotherapies 000839529 5058_ $$a2.2 The Promise of Targeted Cancer Treatment2.3 The DNA Damage Response (DDR); 2.4 Oncogenes Cause Genomic Instability and DDR Activation; 2.5 Tumor Suppression Through Checkpoint Activation and DNA Repair; 2.6 Targeting HR and ATM Deficiencies with PARP and DNA-PK Inhibition; 2.7 Targeting Oncogenic Stress, ATM-p53 Loss, and HR Deficiency with ATR, CHK1 and WEE1 Inhibitors; 2.8 Future Areas of Research; References; Chapter 3: Control of DNA Replication by ATR; 3.1 Introduction; 3.2 ATR Is a PI3K-Related Kinase (PIKK); 3.3 ATR Activation 000839529 5058_ $$a3.3.1 First Step: ssDNA Recruits the ATR-ATRIP Complex3.3.2 Second Step: TOPBP1 Is Necessary for Full Activation of ATR-ATRIP; 3.3.3 Third Step: CLASPIN Is an Adaptor for CHK1 Phosphorylation; 3.3.4 Fine Tuning: Post-Translational Modifications Regulate the Activation of ATR-ATRIP; 3.4 Local, Regional and Global Checkpoint Functions of ATR-ATRIP; 3.4.1 Local Action of ATR-ATRIP on Replication Forks; 3.4.2 Regional Modulation of Replication Factories; 3.4.3 Global Regulation of DNA Replication and the Cell Cycle; 3.5 Functions of ATR and CHK1 in Cancer; 3.5.1 ATR and CHK1 Are Essential 000839529 5058_ $$a3.5.2 Malignant Transformation Generates Replication Stress3.5.3 The Replication Stress Response Favours Malignant Transformation; 3.5.4 Targeting the Replication Stress Response in Cancer; 3.6 Concluding Remarks; References; Chapter 4: Targeting ATR for Cancer Therapy: Profile and Expectations for ATR Inhibitors; 4.1 Role of ATR in the DNA Damage Response; 4.1.1 ATR Signaling to Regulate DNA Replication and Cell Cycle Progression; 4.1.2 ATR Signaling to DNA Repair; 4.2 Validation of ATR as a Therapeutic Target; 4.3 Development of ATR Inhibitors 000839529 5058_ $$a4.4 ATR Inhibition as Combination Therapy with DNA Damaging Chemotherapy4.5 ATR Inhibition as Combination Therapy with Ionising Radiation (IR); 4.6 ATR Inhibition as Monotherapy; 4.7 ATR Inhibition in Combination with Targeted Drugs; 4.8 Conclusion; References; Chapter 5: Targeting ATR for Cancer Therapy: ATR-Targeted Drug Candidates; 5.1 Background; 5.2 Current Clinical Candidates; 5.2.1 VX-970 (M6620); 5.2.1.1 NCT02157792: First-in-Human Study of VX-970 (M6620) in Combination with Cytotoxic Chemotherapy; 5.2.2 AZD6738 000839529 506__ $$aAccess limited to authorized users. 000839529 588__ $$aOnline resource; title from PDF title page (SpringerLink, viewed May 31, 2018). 000839529 650_0 $$aCancer$$xTreatment$$xGenetic aspects. 000839529 650_0 $$aDNA damage. 000839529 7001_ $$aPollard, John,$$eeditor. 000839529 7001_ $$aCurtin, Nicola J.,$$eeditor. 000839529 830_0 $$aCancer drug discovery and development. 000839529 852__ $$bebk 000839529 85640 $$3SpringerLink$$uhttps://univsouthin.idm.oclc.org/login?url=http://link.springer.com/10.1007/978-3-319-75836-7$$zOnline Access$$91397441.1 000839529 909CO $$ooai:library.usi.edu:839529$$pGLOBAL_SET 000839529 980__ $$aEBOOK 000839529 980__ $$aBIB 000839529 982__ $$aEbook 000839529 983__ $$aOnline 000839529 994__ $$a92$$bISE