Directing the use of DDR kinase inhibitors in cancer treatment

References

• Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411:366–374.
   PubMed Web of Science ®Google Scholar
• Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature. 2012;481:287–294.
   PubMed Web of Science ®Google Scholar
• Rundle S, Bradbury A, Drew Y, et al. Targeting the ATR-CHK1 axis in cancer therapy. Cancers (Basel). 2017;9:41.
   Web of Science ®Google Scholar
• Otto T, Sicinski P. Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer. 2017;17:93–115.
   PubMed Web of Science ®Google Scholar
• Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat Rev Mol Cell Biol. 2013;14:197–210.
   Web of Science ®Google Scholar
• Bhattacharya S, Srinivasan K, Abdisalaam S, et al. RAD51 interconnects between DNA replication, DNA repair and immunity. Nucleic Acids Res. 2017;45:4590–4605.
   PubMed Web of Science ®Google Scholar
• Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–421.
   PubMed Web of Science ®Google Scholar
• Kersten K, de Visser KE, van Miltenburg MH, et al. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med. 2016;9:137–153.
   Web of Science ®Google Scholar
• Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–674.
   PubMed Web of Science ®Google Scholar
• McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168:613–628.
   PubMed Web of Science ®Google Scholar
• Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461:1071–1078.
   PubMed Web of Science ®Google Scholar
• Karakaidos P, Zacharatos P, Kotsinas A, et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature. 2005;434:907–913.
   PubMed Web of Science ®Google Scholar
• Bartkova J, Rezaei N, Liontos M, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature. 2006;444:633–637.
   PubMed Web of Science ®Google Scholar
• Toledo LI, Murga M, Zur R, et al. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol. 2011;18:721–727.
   PubMed Web of Science ®Google Scholar
• Zeman MK, Cimprich KA. Causes and consequences of replication stress. Nat Cell Biol. 2014;16:2–9.
   PubMed Web of Science ®Google Scholar
• Drean A, Lord CJ, Ashworth A. PARP inhibitor combination therapy. Crit Rev Oncol. 2016;108:73–85.
   PubMed Web of Science ®Google Scholar
• Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science (80-.). 2017;355:1152–1158.
   PubMed Web of Science ®Google Scholar
• Lavin MF, Khanna KK, Beamish H, et al. Relationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3- kinase. Trends Biochem Sci. 1995;20:382–383.
   PubMed Web of Science ®Google Scholar
• Batey MA, Zhao Y, Kyle S, et al. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther. 2013;12:959–967.
   PubMed Web of Science ®Google Scholar
• Biddlestone-Thorpe L, Sajjad M, Rosenberg E, et al. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin Cancer Res. 2013;19:3189–3200.
   PubMed Web of Science ®Google Scholar
• Williamson CT, Kubota E, Hamill JD, et al. Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53. EMBO Mol Med. 2012;4:515–527.
   PubMed Web of Science ®Google Scholar
• Menezes DL, Holt J, Tang Y, et al. A synthetic lethal screen reveals enhanced sensitivity to ATR Inhibitor treatment in mantle cell lymphoma with ATM loss-of-function. Mol Cancer Res 2014;13: pii: molcanres.0240.2014:120–129.
   PubMed Web of Science ®Google Scholar
• Reaper PM, Griffiths MR, Long JM, et al. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011;7:428–430.
   PubMed Web of Science ®Google Scholar
• Cui Y, Palii SS, Innes CL, et al. Depletion of ATR selectively sensitizes atmdeficient human mammary epithelial cells to ionizing radiation and DNA-damaging agents. Cell Cycle. 2014;13:3541–3550.
   PubMed Web of Science ®Google Scholar
• Shen JP, Zhao D, Sasik R, et al. Combinatorial CRISPR–Cas9 screens for de novo mapping of genetic interactions. Nat Methods. 2017;14:573–576.
   Web of Science ®Google Scholar
• Mohni KN, Kavanaugh GM, Cortez D. ATR pathway inhibition is synthetically lethal in cancer cells with ercc1 deficiency. Cancer Res. 2014;74:2835–2845.
   PubMed Web of Science ®Google Scholar
• Foote KM, Blades K, Cronin A, et al. Discovery of -{4-[(3R)‑3-Methylmorpholin-4-yl]-6-[1- (methylsulfonyl)cyclopropyl]pyrimidin-2-yl}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J Med Chem. 2013;56:2125–2138.
   PubMed Web of Science ®Google Scholar
• Kwok M, Davies N, Agathanggelou A, et al. ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53 or ATM defective chronic lymphocytic leukemia cells. Blood. 2016;127:582–595.
   PubMed Web of Science ®Google Scholar
• Hocke S, Guo Y, Job A, et al. A synthetic lethal screen identifies ATR-inhibition as a novel therapeutic approach for POLD1-deficient cancers. Oncotarget. 2016;7:7080–7095.
   PubMed Web of Science ®Google Scholar
• Williamson CT, Miller R, Pemberton HN, et al. ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. Nat Commun. 2016;7:13837.
   PubMed Web of Science ®Google Scholar
• Flynn RL, Cox KE, Jeitany M, et al. Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science (80-.). 2015;347:273–277.
   PubMed Web of Science ®Google Scholar
• Deeg KI, Chung I, Bauer C, et al. Cancer cells with alternative lengthening of telomeres do not display a general hypersensitivity to ATR inhibition. Front Oncol. 2016;6:0–13.
   Web of Science ®Google Scholar
• Nieto-Soler M, Morgado-Palacin I, Lafarga V, et al. Efficacy of ATR inhibitors as single agents in Ewing sarcoma. Oncotarget. 2016;7:58759–58767.
   PubMed Web of Science ®Google Scholar
• Jones S, Fleuren E, Frankum J. ATR is a therapeutic target in synovial sarcoma. Cancer Res. in press.
   Web of Science ®Google Scholar
• Mohni KN, Thompson PS, Luzwick JW, et al. A synthetic lethal screen identifies DNA repair pathways that sensitize cancer cells to combined ATR inhibition and cisplatin treatments. PLoS One. 2015;10:e0125482.
   Web of Science ®Google Scholar
• Riabinska A, Daheim M, Herter-Sprie GS, et al. Therapeutic targeting of a robust non-oncogene addiction to PRKDC in ATM-defective tumors. Sci Transl Med. 2013;5:189ra78.
   PubMed Web of Science ®Google Scholar
• Chen Z, Xiao Z, Gu WZ, et al. Selective Chk1 inhibitors differentially sensitize p53-deficient cancer cells to cancer therapeutics. Int J Cancer. 2006;119:2784–2794.
   PubMed Web of Science ®Google Scholar
• Bridges KA, Chen X, Liu H, et al. MK-8776, a novel chk1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Oncotarget. 2016;15:71660–71672.
   Google Scholar
• Zhang Y, Hunter T. Roles of Chk1 in cell biology and cancer therapy. Int J Cancer. 2014;134:1013–1023.
   PubMed Web of Science ®Google Scholar
• Scagliotti G, Kang J, Smith D, et al. Phase II evaluation of LY2603618, a first-generation CHK1 inhibitor, in combination with pemetrexed in patients with advanced or metastatic non-small cell lung cancer. Invest New Drugs. 2016;34:625–635.
   PubMed Web of Science ®Google Scholar
• Dietlein F, Kalb B, Jokic M, et al. A synergistic interaction between Chk1- and MK2 inhibitors in KRAS-mutant cancer. Cell. 2015;162:146–159.
   PubMed Web of Science ®Google Scholar
• Hirai H, Iwasawa Y, Okada M, et al. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther. 2009;8:2992–3000.
   PubMed Web of Science ®Google Scholar
• Aarts M, Sharpe R, Garcia-Murillas I, et al. Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. Cancer Discov. 2012;2:524–539.
   PubMed Web of Science ®Google Scholar
• Guertin AD, Li J, Liu Y, et al. Preclinical evaluation of the WEE1 inhibitor MK-1775 as single-agent anticancer therapy. Mol Cancer Ther. 2013;12:1442–1452.
   PubMed Web of Science ®Google Scholar
• Lal S, Zarei M, Chand SN, et al. WEE1 inhibition in pancreatic cancer cells is dependent on DNA repair status in a context dependent manner. Sci Rep. 2016;6:33323.
   PubMed Web of Science ®Google Scholar
• Pfister SX, Markkanen E, Jiang Y, et al. Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation. Cancer Cell. 2015;28:557–568.
   PubMed Web of Science ®Google Scholar
• Weisberg E, Nonami A, Chen Z, et al. Identification of wee1 as a novel therapeutic target for mutant RAS-driven acute leukemia and other malignancies. Leukemia. 2014;29:27–37.
   PubMed Web of Science ®Google Scholar
• Dai Y, Grant S. New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res. 2010;16:376–383.
   PubMed Web of Science ®Google Scholar
• Zannini L, Delia D, Buscemi G. CHK2 kinase in the DNA damage response and beyond. J Mol Cell Biol. 2014;6:442–457.
   PubMed Web of Science ®Google Scholar
• Tresini M, Warmerdam DO, Kolovos P, et al. The core spliceosome as target and effector of non-canonical ATM signalling. Nature. 2015;523:53–58.
   PubMed Web of Science ®Google Scholar
• Beà S, Valdés-Mas R, Navarro A, et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci USA. 2013;110:18250–18255.
   PubMed Web of Science ®Google Scholar
• Hickson I, Zhao Y, Richardson CJ, et al. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res. 2004;64:9152–9159.
   PubMed Web of Science ®Google Scholar
• Golding SE, Rosenberg E, Valerie N, et al. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009;8:2894–2902.
   PubMed Web of Science ®Google Scholar
• Weber AM, Ryan AJ. ATM and ATR as therapeutic targets in cancer. Pharmacol Ther. 2015;149:124–138.
   PubMed Web of Science ®Google Scholar
• Pike KG. Identifying high quality, potent and selective inhibtors of ATM kinase: discovery of AZD0156. Proceeding 107th Annual Meeting if American Association Cancer Research. New Orleans, LA, USA, April 2016.
   Google Scholar
• Brown JS, OCarrigan B, Jackson SP, et al. Targeting DNA repair in cancer: beyond PARP inhibitors. Cancer Discov. 2016;7:20–38.
   PubMed Web of Science ®Google Scholar
• Chaudhuri L, Vincelette ND, Koh BD, et al. CHK1 and WEE1 inhibition combine synergistically to enhance therapeutic efficacy in acute myeloid leukemia ex vivo. Haematologica. 2014;99:688–696.
   PubMed Web of Science ®Google Scholar
• Magnussen GI, Emilsen E, Giller Fleten K, et al. Combined inhibition of the cell cycle related proteins Wee1 and Chk1/2 induces synergistic anti-cancer effect in melanoma. BMC Cancer. 2015;15:462.
   PubMed Web of Science ®Google Scholar
• Jobson AG, Lountos GT, Lorenzi PL, et al. Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of camptothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. J Pharmacol Exp Ther. 2009;331:816–826.
   PubMed Web of Science ®Google Scholar
• Anderson VE, Walton MI, Eve PD, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011;71:463–472.
   PubMed Web of Science ®Google Scholar
• Zabludoff SD, Deng C, Grondine MR, et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther. 2008;7:2955–2966.
   PubMed Web of Science ®Google Scholar
• Morgan MA, Parsels LA, Zhao L, et al. Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res. 2010;70:4972–4981.
   PubMed Web of Science ®Google Scholar
• Carrassa L, Chilà R, Lupi M, et al. Combined inhibition of Chk1 and Wee1: in vitro synergistic effect translates to tumor growth inhibition in vivo. Cell Cycle. 2012;11:2507–2517.
   PubMed Web of Science ®Google Scholar
• Jhuraney A, Woods NT, Wright G, et al. PAXIP1 potentiates the combination of WEE1 inhibitor AZD1775 and platinum agents in lung cancer. Mol Cancer Ther. 2016;1669–1681.
   PubMed Web of Science ®Google Scholar
• Ford JB, Baturin D, Burleson TM, et al. AZD1775 sensitizes T cell acute lymphoblastic leukemia cells to cytarabine by promoting apoptosis over DNA repair. Oncotarget. 2015;6:28001–28010.
   Google Scholar
• Wang G, Niu X, Zhang W, et al. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015;356:656–668.
   PubMed Web of Science ®Google Scholar
• Nakayama Y, Igarashi A, Kikuchi I, et al. Bleomycin-induced over-replication involves sustained inhibition of mitotic entry through the ATM/ATR pathway. Exp Cell Res. 2009;315:2515–2528.
   PubMed Web of Science ®Google Scholar
• Hsiang YH, Lihou MG, Liu LF. Arrest of replication forks by Drug-stabilized Topoisomerase I-DNA cleavable complexes as a mechanism of cell killing by camptothecin. Cancer Res. 1989;49:5077–5082.
   PubMed Web of Science ®Google Scholar
• Sartori AA, Lukas C, Coates J, et al. Human CtIP promotes DNA end resection. Nature. 2007;450:509–514.
   PubMed Web of Science ®Google Scholar
• Bakr A, Oing C, Köcher S, et al. Involvement of ATM in homologous recombination after end resection and RAD51 nucleofilament formation. Nucleic Acids Res. 2015;43:3154–3166.
   PubMed Web of Science ®Google Scholar
• Williamson C, Muzik H, Turhan A. ATM deficiency sensitizes mantle cell lymphoma cells to poly (ADP-ribose) polymerase-1 inhibitors. Mol Cancer Ther. 2010;9:347–357.
   PubMed Web of Science ®Google Scholar
• McCabe N, Turner NC, Lord CJ, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. 2006;66:8109–8115.
   PubMed Web of Science ®Google Scholar
• Bunting SF, Callén E, Wong N, et al. 53BP1 inhibits homologous recombination in brca1-deficient cells by blocking resection of DNA breaks. Cell. 2010;141:243–254.
   PubMed Web of Science ®Google Scholar
• Xu G, Chapman JR, Brandsma I, et al. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature. 2015;521:541–544.
   PubMed Web of Science ®Google Scholar
• Lecona E, Fernández-Capetillo O. Replication stress and cancer: it takes two to tango. Exp Cell Res. 2014;329:26–34.
   PubMed Web of Science ®Google Scholar
• Yazinski SA, Zou L. Functions, regulation, and therapeutic implications of the ATR checkpoint pathway. Annu Rev Genet. 2015;50:1–19.
   PubMed Web of Science ®Google Scholar
• Lee J, Kumagai A, Dunphy WG. Positive regulation of Wee1 by Chk1 and 14-3-3 proteins. Mol Biol Cell. 2001;12:551–563.
   PubMed Web of Science ®Google Scholar
• Parker LL, Piwnica-Worms H. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science (80-.). 1992;257:1955–1957.
   PubMed Web of Science ®Google Scholar
• Charrier JD, Durrant SJ, Golec JMC, et al. Discovery of potent and selective inhibitors of Ataxia Telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J Med Chem. 2011;54:2320–2330.
   PubMed Web of Science ®Google Scholar
• Fokas E, Prevo R, Pollard JR, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012;3:e441.
   PubMed Web of Science ®Google Scholar
• Karnitz LM, Zou L. Molecular pathways: targeting ATR in cancer therapy. Clin Cancer Res. 2015;21:4780–4785.
   PubMed Web of Science ®Google Scholar
• Peasland A, Wang L-Z, Rowling E, et al. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer. 2011;105:372–381.
   PubMed Web of Science ®Google Scholar
• Prevo R, Fokas E, Reaper PM, et al. The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012;13:1072–1081.
   PubMed Web of Science ®Google Scholar
• Huntoon CJ, Flatten KS, Wahner Hendrickson AE, et al. ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status. Cancer Res. 2013;73:3683–3691.
   PubMed Web of Science ®Google Scholar
• Jossé R, Martin SE, Guha R, et al. ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase I inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014;74:6968–6978.
   PubMed Web of Science ®Google Scholar
• Biskup E, Naym DG, Gniadecki R. Small-molecule inhibitors of Ataxia Telangiectasia and Rad3 related kinase (ATR) sensitize lymphoma cells to UVA radiation. J Dermatol Sci. 2016;84:3.
   Web of Science ®Google Scholar
• Sanjiv K, Hagenkort A, Calderón-Montaño JM, et al. Cancer-specific synthetic lethality between ATR and CHK1 kinase activities. Cell Rep. 2016;14:298–309.
   PubMed Web of Science ®Google Scholar
• Huang KK, Jang KW, Kim S, et al. Exome sequencing reveals recurrent REV3L mutations in cisplatin-resistant squamous cell carcinoma of head and neck. Sci Rep. 2016;6:19552.
   PubMed Web of Science ®Google Scholar
• Kadoch C, Hargreaves DC, Hodges C, et al. Proteomic and bioinformatic analysis of mammalian SWI/SNF complexes identifies extensive roles in human malignancy. Nat Genet. 2013;45:592–601.
   PubMed Web of Science ®Google Scholar
• Colicchia V, Petroni M, Guarguaglini G, et al. PARP inhibitors enhance replication stress and cause mitotic catastrophe in MYCN-dependent neuroblastoma. Oncogene. 2017;36:4682–4691.
   PubMed Web of Science ®Google Scholar
• Mouw KW, Goldberg MS, Konstantinopoulos PA, et al. DNA damage and repair biomarkers of immunotherapy response. Cancer Discov. 2017;7:617–632.
   Web of Science ®Google Scholar
• Ruiz S, Mayor-Ruiz C, Lafarga V, et al. A genome-wide CRISPR screen identifies CDC25A as a determinant of sensitivity to ATR inhibitors. Mol Cell. 2016;62:307–313.
   PubMed Web of Science ®Google Scholar
• Jette N, Lees-Miller SP. The DNA-dependent protein kinase: a multifunctional protein kinase with roles in DNA double strand break repair and mitosis. Prog Biophys Mol Biol. 2015;117:194–205.
   PubMed Web of Science ®Google Scholar
• van der Burg M, van Dongen JJM, van Gent DC. DNA-PKcs deficiency in human: long predicted, finally found. Curr Opin Allergy Clin Immunol. 2009;9:503–509.
   PubMed Web of Science ®Google Scholar
• Beskow C, Skikuniene J, Holgersson A, et al. Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86. Br J Cancer. 2009;101:816–821.
   PubMed Web of Science ®Google Scholar
• Bouchaert P, Guerif S, Debiais C, et al. DNA-PKcs expression predicts response to radiotherapy in prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84:1179–1185.
   PubMed Web of Science ®Google Scholar
• Austen B, Powell JE, Alvi A, et al. Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL. Blood. 2005;106:3175–3182.
   PubMed Web of Science ®Google Scholar
• Zhou Z, Patel M, Ng N, et al. Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening. BMC Cancer. 2014;14:944.
   PubMed Web of Science ®Google Scholar
• Dietlein F, Thelen L, Jokic M, et al. A functional cancer genomics screen identifies a druggable synthetic lethal interaction between MSH3 and PRKDC. Cancer Discov. 2014;4:592–605.
   PubMed Web of Science ®Google Scholar
• Baumann M, Krause M, Overgaard J, et al. Radiation oncology in the era of precision medicine. Nat Rev Cancer. 2016;16:234–249.
   PubMed Web of Science ®Google Scholar
• Patel AG, Sarkaria JN, Kaufmann SH. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc Natl Acad Sci USA. 2011;108:3406–3411.
   PubMed Web of Science ®Google Scholar
• Gatei M, Sloper K, Sörensen C, et al. Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation. J Biol Chem. 2003;278:14806–14811.
   PubMed Web of Science ®Google Scholar
• Busino L, Donzelli M, Chiesa M, et al. Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature. 2003;426:87–91.
   PubMed Web of Science ®Google Scholar
• Sanchez Y, Wong C, Thoma RS, et al. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science. 1997;277:1497–1501.
   PubMed Web of Science ®Google Scholar
• Calvo E, Chen V, Marshall M, et al. Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer. Invest New Drugs. 2014;32:955–968.
   PubMed Web of Science ®Google Scholar
• Karp JE, Thomas BM, Greer JM, et al. Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias. Clin Cancer Res. 2012;18:6723–6731.
   PubMed Web of Science ®Google Scholar
• Rawlinson R, Massey AJ. γH2AX and Chk1 phosphorylation as predictive pharmacodynamic biomarkers of Chk1 inhibitor-chemotherapy combination treatments. BMC Cancer. 2014;14:483.
   PubMed Web of Science ®Google Scholar
• Bryant C, Rawlinson R, Massey AJ. Chk1 inhibition as a novel therapeutic strategy for treating triple-negative breast and ovarian cancers. BMC Cancer. 2014;14:1–14.
   Web of Science ®Google Scholar
• Xiao Z, Xue J, Gu W-Z, et al. Cyclin B1 is an efficacy-predicting biomarker for Chk1 inhibitors. Biomarkers. 2008;13:579–596.
   PubMed Web of Science ®Google Scholar
• Sakurikar N, Thompson R, Montano R, et al. A subset of cancer cell lines is acutely sensitive to the Chk1 inhibitor MK-8776 as monotherapy due to CDK2 activation in S phase. Oncotarget. 2016;7:1380–1394.
   PubMed Web of Science ®Google Scholar
• Matthews DJ, Yakes FM, Chen J, et al. Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo. Cell Cycle. 2007;6:104–110.
   PubMed Web of Science ®Google Scholar
• Ahn JY, Li X, Davis HL, et al. Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain. J Biol Chem. 2002;277:19389–19395.
   PubMed Web of Science ®Google Scholar
• Bartek J, Falck J, Lukas J. CHK2 kinase–a busy messenger. Nat Rev Mol Cell Biol. 2001;2:877–886.
   PubMed Web of Science ®Google Scholar
• Caldwell JJ, Welsh EJ, Matijssen C, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011;54:580–590.
   PubMed Web of Science ®Google Scholar
• Sausville E, LoRusso P, Carducci M, et al. Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors. Cancer Chemother Pharmacol. 2014;73:539–549.
   PubMed Web of Science ®Google Scholar
• Watanabe N, Arai H, Nishihara Y, et al. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci USA. 2004;101:4419–4424.
   PubMed Web of Science ®Google Scholar
• Osman AA, Monroe MM, Ortega Alves MV, et al. Wee-1 kinase inhibition overcomes cisplatin resistance associated with high-risk TP53 mutations in head and neck cancer through mitotic arrest followed by senescence. Mol Cancer Ther. 2015;14:608–619.
   PubMed Web of Science ®Google Scholar
• Chila R, Basana A, Lupi M, et al. Combined inhibition of Chk1 and Wee1 as a new therapeutic strategy for mantle cell lymphoma. Oncotarget. 2015;6:3394–3408.
   PubMed Web of Science ®Google Scholar
• Edwards SL, Brough R, Lord CJ, et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature. 2008;451:1111–1115.
   PubMed Web of Science ®Google Scholar
• Sakai W, Swisher EM, Karlan BY, et al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature. 2008;451:1116–1120.
   PubMed Web of Science ®Google Scholar
• Drean A, Williamson CT, Brough R, et al. Modelling therapy resistance in BRCA1/2 mutant cancers. Mol Cancer Ther. 2017. molcanther.0098.2016.
   PubMed Web of Science ®Google Scholar
• Do K, Wilsker D, Ji J, et al. Phase I study of single-agent AZD1775 (MK-1775), a wee1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol. 2015;33:3409–3415.
   PubMed Web of Science ®Google Scholar
• Leijen S, Rmjm VG, Sonke GS, et al. Phase II study of WEE1 inhibitor AZD1775 plus carboplatin in patients with TP53-mutated ovarian cancer refractory or resistant to first-line therapy within 3 months. J Clin Oncol. 2016. JCO.2016.67.5942.
   Web of Science ®Google Scholar
• Restelli V, Chilà R, Lupi M, et al. Characterization of a mantle cell lymphoma cell line resistant to the Chk1 inhibitor PF-00477736. Oncotarget. 2015;6:37229–37240.
   PubMed Web of Science ®Google Scholar
• Li Y, Saini P, Sriraman A, et al. Mdm2 inhibition confers protection of p53-proficient cells from the cytotoxic effects of Wee1 inhibitors. Oncotarget. 2015;6:32339–32352.
   PubMed Web of Science ®Google Scholar
• Kwak EL, Sordella R, Bell DW, et al. Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib. Source Proc Natl Acad Sci United States Am. 2005;102:7665–7670.
   PubMed Web of Science ®Google Scholar
• Nakad R, Schumacher B. DNA damage response and immune defense: links and mechanisms. Front Genet. 2016;7:147.
   PubMed Web of Science ®Google Scholar
• Kyi C, Postow MA. Checkpoint blocking antibodies in cancer immunotherapy. FEBS Lett. 2014;588:368–376.
   PubMed Web of Science ®Google Scholar
• Parkes EE, Walker SM, Taggart LE, et al. Activation of STING-dependent innate immune signaling by s-phase-specific DNA damage in breast cancer. J Natl Cancer Inst. 2017;6:dwj199.
   PubMedGoogle Scholar
• Lennerz V, Fatho M, Gentilini C, et al. The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc Natl Acad Sci USA. 2005;102:16013–16018.
   PubMed Web of Science ®Google Scholar