39
Views
0
CrossRef citations to date
0
Altmetric
REVIEW

Targeting WEE1 Kinase in Gynecological Malignancies

, &
Pages 2449-2460 | Received 31 Jan 2024, Accepted 27 May 2024, Published online: 20 Jun 2024

References

  • Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature. 2004;432(7015):316–323. doi:10.1038/nature03097
  • Beck H, Nähse-Kumpf V, Larsen MS, et al. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol Cell Biol. 2012;32(20):4226–4236. doi:10.1128/mcb.00412-12
  • Moiseeva TN, Qian C, Sugitani N, Osmanbeyoglu HU, Bakkenist CJ. WEE1 kinase inhibitor AZD1775 induces CDK1 kinase-dependent origin firing in unperturbed G1- and S-phase cells. Proc Natl Acad Sci USA. 2019;116(48):23891–23893. doi:10.1073/pnas.1915108116
  • Kellogg DR. Wee1-dependent mechanisms required for coordination of cell growth and cell division. J Cell Sci. 2003;116(Pt 24):4883–4890. doi:10.1242/jcs.00908
  • Domínguez-Kelly R, Martín Y, Koundrioukoff S, et al. Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease. J Cell Biol. 2011;194(4):567–579. doi:10.1083/jcb.201101047
  • Krajewska M, Heijink AM, Bisselink YJ, et al. Forced activation of Cdk1 via wee1 inhibition impairs homologous recombination. Oncogene. 2013;32(24):3001–3008. doi:10.1038/onc.2012.296
  • Cole AJ, Dwight T, Gill AJ, et al. Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing. Sci Rep. 2016;6:26191. doi:10.1038/srep26191
  • Kandoth C, Schultz N, Cherniack AD, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73. doi:10.1038/nature12113
  • Werness BA, Levine AJ, Howley PM. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990;248(4951):76–79. doi:10.1126/science.2157286
  • Jazayeri A, Falck J, Lukas C, et al. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol. 2006;8(1):37–45. doi:10.1038/ncb1337
  • Elbæk CR, Petrosius V, Sørensen CS. WEE1 kinase limits CDK activities to safeguard DNA replication and mitotic entry. Mutat Res. 2020;819-820:111694. doi:10.1016/j.mrfmmm.2020.111694
  • Guimaraes DP, Hainaut P. TP53: a key gene in human cancer. Biochimie. 2002;84(1):83–93. doi:10.1016/s0300-9084(01)01356-6
  • Matheson CJ, Backos DS, Reigan P. Targeting WEE1 Kinase in Cancer. Trends Pharmacol Sci. 2016;37(10):872–881. doi:10.1016/j.tips.2016.06.006
  • 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(11):2992–3000. doi:10.1158/1535-7163.mct-09-0463
  • Wang Y, Li J, Booher RN, et al. Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Res. 2001;61(22):8211–8217.
  • Palmer BD, Thompson AM, Booth RJ, et al. 4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione inhibitors of the checkpoint kinase Wee1. Structure-activity relationships for chromophore modification and phenyl ring substitution. J Med Chem. 2006;49(16):4896–4911. doi:10.1021/jm0512591
  • Huang PQ, Boren BC, Hegde SG, et al. Discovery of ZN-c3, a Highly Potent and Selective Wee1 Inhibitor Undergoing Evaluation in Clinical Trials for the Treatment of Cancer. J Med Chem. 2021;64(17):13004–13024. doi:10.1021/acs.jmedchem.1c01121
  • Gelderblom H, Gietema JA, Desar IME, et al. 601TiP First-in-human phase I study of a novel oral Wee1 inhibitor (Debio 0123) in combination with carboplatin in patients with advanced solid tumours. Ann Oncol. 2020;31:S501–2. doi:10.1016/j.annonc.2020.08.715
  • Lin -C-C, Grewal JS, Sommerhalder D, et al. A Phase 1 dose-escalation and -expansion study of IMP7068, a WEE1 inhibitor, in patients with advanced solid tumors. J clin oncol. 2022;40(16_suppl):e15052. doi:10.1200/JCO.2022.40.16_suppl.e15052
  • Leijen S, van Geel RM, 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;34(36):4354–4361. doi:10.1200/jco.2016.67.5942
  • Oza AM, Estevez-Diz M, Grischke EM, et al. A Biomarker-enriched, Randomized Phase II Trial of Adavosertib (AZD1775) Plus Paclitaxel and Carboplatin for Women with Platinum-sensitive TP53-mutant Ovarian Cancer. Clin Cancer Res. 2020;26(18):4767–4776. doi:10.1158/1078-0432.ccr-20-0219
  • Lheureux S, Cristea MC, Bruce JP, et al. Adavosertib plus gemcitabine for platinum-resistant or platinum-refractory recurrent ovarian cancer: a double-blind, randomised, placebo-controlled, Phase 2 trial. Lancet. 2021;397(10271):281–292. doi:10.1016/s0140-6736(20)32554-x
  • Moore KN, Chambers SK, Hamilton EP, et al. Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: an Open-Label, Four-Arm, Phase II Study. Clin Cancer Res. 2022;28(1):36–44. doi:10.1158/1078-0432.Ccr-21-0158
  • Liu J, Oza AM, Colombo N, Oaknin A. ADAGIO: a phase IIb international study of the Wee1 inhibitor adavosertib in women with recurrent or persistent uterine serous carcinoma. Int J Gynecol Cancer. 2022;32(1):89–92. doi:10.1136/ijgc-2021-003144
  • Meng X, Bi J, Li Y, et al. AZD1775 Increases Sensitivity to Olaparib and Gemcitabine in Cancer Cells with p53 Mutations. Cancers. 2018;10(5):149.
  • Zhang M, Dominguez D, Chen S, et al. WEE1 inhibition by MK1775 as a single-agent therapy inhibits ovarian cancer viability. Oncol Lett. 2017;14(3):3580–3586. doi:10.3892/ol.2017.6584
  • Li J, Wang Y, Sun Y, Lawrence TS. Wild-type TP53 inhibits G(2)-phase checkpoint abrogation and radiosensitization induced by PD0166285, a WEE1 kinase inhibitor. Radiation Res. 2002;157(3):322–330. doi:10.1667/0033-7587(2002)157
  • Lee YY, Cho YJ, Shin SW, et al. Anti-Tumor Effects of Wee1 Kinase Inhibitor with Radiotherapy in Human Cervical Cancer. Sci Rep. 2019;9(1):15394. doi:10.1038/s41598-019-51959-3
  • Cuneo KC, Morgan MA, Davis MA, et al. Wee1 Kinase Inhibitor AZD1775 Radiosensitizes Hepatocellular Carcinoma Regardless of TP53 Mutational Status Through Induction of Replication Stress. Int J Radiat Oncol Biol Phys. 2016;95(2):782–790. doi:10.1016/j.ijrobp.2016.01.028
  • Chiappa M, Guffanti F, Anselmi M, et al. Combinations of ATR, Chk1 and Wee1 Inhibitors with Olaparib Are Active in Olaparib Resistant Brca1 Proficient and Deficient Murine Ovarian Cells. Cancers. 2022;14(7):1807.
  • Fang Y, McGrail DJ, Sun C, et al. Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy. Cancer Cell. 2019;35(6):851–867.e7. doi:10.1016/j.ccell.2019.05.001
  • Xu H, George E, Kinose Y, et al. CCNE1 copy number is a biomarker for response to combination WEE1-ATR inhibition in ovarian and endometrial cancer models. Cell Rep Med. 2021;2(9):100394. doi:10.1016/j.xcrm.2021.100394
  • Wu X, Kang X, Zhang X, et al. WEE1 inhibitor and ataxia telangiectasia and RAD3-related inhibitor trigger stimulator of interferon gene-dependent immune response and enhance tumor treatment efficacy through programmed death-ligand 1 blockade. Cancer Sci. 2021;112(11):4444–4456. doi:10.1111/cas.15108
  • Gonzalez-Ochoa E, Milosevic M, Corr B, et al. A phase I study of the Wee1 kinase inhibitor adavosertib (AZD1775) in combination with chemoradiation in cervical, upper vaginal, and uterine cancers. Int J Gynecol Cancer. 2023;33(8):1208–1214. doi:10.1136/ijgc-2023-004491
  • Slipicevic A, Holth A, Hellesylt E, Tropé CG, Davidson B, Flørenes VA. Wee1 is a novel independent prognostic marker of poor survival in post-chemotherapy ovarian carcinoma effusions. Gynecol Oncol. 2014;135(1):118–124. doi:10.1016/j.ygyno.2014.07.102
  • Iorns E, Lord CJ, Grigoriadis A, et al. Integrated functional, gene expression and genomic analysis for the identification of cancer targets. PLoS One. 2009;4(4):e5120. doi:10.1371/journal.pone.0005120
  • Magnussen GI, Hellesylt E, Nesland JM, Trope CG, Flørenes VA, Holm R. High expression of wee1 is associated with malignancy in vulvar squamous cell carcinoma patients. BMC Cancer. 2013;13:288. doi:10.1186/1471-2407-13-288
  • Li J, Lu J, Xu M, et al. ODF2L acts as a synthetic lethal partner with WEE1 inhibition in epithelial ovarian cancer models. J Clin Invest. 2023;133(2).
  • PosthumaDeBoer J, Würdinger T, Graat HC, et al. WEE1 inhibition sensitizes osteosarcoma to radiotherapy. BMC Cancer. 2011;29(11):156. doi:10.1186/1471-2407-11-156
  • Esposito F, Giuffrida R, Raciti G, Puglisi C, Forte S. Wee1 Kinase: a Potential Target to Overcome Tumor Resistance to Therapy. Int J Mol Sci. 2021;22(19).
  • Mir SE, De Witt Hamer PC, Krawczyk PM, et al. In silico analysis of kinase expression identifies WEE1 as a gatekeeper against mitotic catastrophe in glioblastoma. Cancer Cell. 2010;18(3):244–257. doi:10.1016/j.ccr.2010.08.011
  • Buisson R, Niraj J, Rodrigue A, et al. Coupling of Homologous Recombination and the Checkpoint by ATR. Mol Cell. 2017;65(2):336–346. doi:10.1016/j.molcel.2016.12.007
  • Li F, Guo E, Huang J, et al. mTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers. Am J Cancer Res. 2020;10(3):908–924.
  • Xiao R, You L, Zhang L, et al. Inhibiting the IRE1α Axis of the Unfolded Protein Response Enhances the Antitumor Effect of AZD1775 in TP53 Mutant Ovarian Cancer. Adv. Sci. 2021:2105469. doi:10.1002/advs.202105469
  • Rosen DG, Yang G, Deavers MT, et al. Cyclin E expression is correlated with tumor progression and predicts a poor prognosis in patients with ovarian carcinoma. Cancer. 2006;106(9):1925–1932. doi:10.1002/cncr.21767
  • Patch AM, Christie EL, Etemadmoghadam D, et al. Whole-genome characterization of chemoresistant ovarian cancer. Nature. 2015;521(7553):489–494. doi:10.1038/nature14410
  • Guo E, Xiao R, Wu Y, et al. WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway. J Exp Med. 2022;219(1).
  • Takebe N, Naqash AR, O’Sullivan Coyne G, et al. Safety, Antitumor Activity, and Biomarker Analysis in a Phase I Trial of the Once-daily Wee1 Inhibitor Adavosertib (AZD1775) in Patients with Advanced Solid Tumors. Clin Cancer Res. 2021;27(14):3834–3844. doi:10.1158/1078-0432.ccr-21-0329
  • Tolcher A, Mamdani H, Chalasani P, et al. Clinical Activity of Single-Agent ZN-c3, an Oral WEE1 Inhibitor, in a Phase 1 Dose-Escalation Trial in Patients with Advanced Solid Tumors. Philadelphia, Pa: AMER ASSOC CANCER RESEARCH 615 CHESTNUT ST, 17TH FLOOR; 2021.
  • Dellino M, Cerbone M, Laganà AS, et al. Upgrading Treatment and Molecular Diagnosis in Endometrial Cancer-Driving New Tools for Endometrial Preservation? Int J Mol Sci. 2023;24(11).
  • McAlpine J, Leon-Castillo A, Bosse T. The rise of a novel classification system for endometrial carcinoma; integration of molecular subclasses. J Pathol. 2018;244(5):538–549. doi:10.1002/path.5034
  • Kandoth C, McLellan MD, Vandin F, et al. Mutational landscape and significance across 12 major cancer types. Nature. 2013;502(7471):333–339. doi:10.1038/nature12634
  • McGunigal M, Liu J, Kalir T, Chadha M, Gupta V. Survival Differences Among Uterine Papillary Serous, Clear Cell and Grade 3 Endometrioid Adenocarcinoma Endometrial Cancers: a National Cancer Database Analysis. Int J Gynecol Cancer. 2017;27(1):85–92. doi:10.1097/igc.0000000000000844
  • Zhao S, Choi M, Overton JD, et al. Landscape of somatic single-nucleotide and copy-number mutations in uterine serous carcinoma. Proc Natl Acad Sci USA. 2013;110(8):2916–2921. doi:10.1073/pnas.1222577110
  • Liu JF, Xiong N, Campos SM, et al. Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma. J Clin Oncol. 2021;39(14):1531–1539. doi:10.1200/jco.20.03167
  • Miwa K, Miyamoto S, Kato H, et al. The role of p53 inactivation in human cervical cell carcinoma development. Br J Cancer. 1995;71(2):219–226. doi:10.1038/bjc.1995.47
  • Benard VB, Thomas CC, King J, Massetti GM, Doria-Rose VP, Saraiya M. Vital signs: cervical cancer incidence, mortality, and screening - United States, 2007-2012. MMWR Morb Mortal Wkly Rep. 2014;63(44):1004–1009.
  • Valenti G, Vitale SG, Tropea A, Biondi A, Laganà AS. Tumor markers of uterine cervical cancer: a new scenario to guide surgical practice? Updates Surg. 2017;69(4):441–449. doi:10.1007/s13304-017-0491-3
  • Schutte T, Embaby A, Steeghs N, et al. Clinical development of WEE1 inhibitors in gynecological cancers: a systematic review. Cancer Treat Rev. 2023;115:102531. doi:10.1016/j.ctrv.2023.102531