Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2016

Open Access 01-12-2016 | Review

Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword

Authors: Roberta Visconti, Rosa Della Monica, Domenico Grieco

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2016

Login to get access

Abstract

Major currently used anticancer therapeutics either directly damage DNA or target and upset basic cell division mechanisms like DNA replication and chromosome segregation. These insults elicit activation of cell cycle checkpoints, safeguard mechanisms that cells implement to correctly complete cell cycle phases, repair damage or eventually commit suicide in case damage is unrepairable. Although cancer cells appear to be advantageously defective in some aspects of checkpoint physiology, recent acquisitions on the biochemical mechanisms of the various checkpoints are offering new therapeutic approaches against cancer. Indeed, chemical manipulation of these mechanisms is providing new therapeutic strategies and tools to increase the killing efficacy of major cancer therapeutics as well as to directly promote cancer cell death. In this review we summarize developing concepts on how targeting cell cycle checkpoints may provide substantial improvement to cancer therapy.
Literature
1.
2.
Visconti R, Grieco D. New insights on oxidative stress in cancer. Curr Opin Drug Discov Devel. 2009;12:240–5.PubMed
3.
Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer. 2012;12:801–17.CrossRefPubMed
4.
Hunter T, Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994;79:573–82.CrossRefPubMed
5.
6.
7.
Mathur R, Chandna S, N Kapoor P, S Dwarakanath B. Peptidyl prolyl isomerase, Pin1 is a potential target for enhancing the therapeutic efficacy of etoposide. Curr Cancer Drug Targets. 2011;11:380–92.CrossRefPubMed
8.
Wan G, Mathur R, Hu X, Liu Y, Zhang X, Peng G, Lu X. Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal. 2013;25:1086–95.CrossRefPubMedPubMedCentral
9.
10.
Bartek J, Lukas J. DNA damage checkpoint: from initiation to recovery or adaptation. Curr Opin Cell Biol. 2007;19:238–45.CrossRefPubMed
11.
Matsuoka S, Huang M, Elledge SJ. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science. 1998;282:1893–7.CrossRefPubMed
12.
Falck J, Mailand N, Syljuåsen RG, Bartek J, Lukas J. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature. 2001;410:842–7.CrossRefPubMed
13.
Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell. 1997;91:325–34.CrossRefPubMed
14.
Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science. 1998;281:1674–7.CrossRefPubMed
15.
Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science. 1998;281:1677–9.CrossRefPubMed
16.
Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993;75:805–16.CrossRefPubMed
17.
el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993;75:817-25.
18.
Gu Y, Turck CW, Morgan DO. Inhibition of CDK2 activity in vivo by an associated 20 K regulatory subunit. Nature. 1993;366:707–10.CrossRefPubMed
19.
20.
Soddu S, Sacchi A. P53 role in DNA repair and tumorigenesis. J Exp Clin Cancer Res. 1997;16:237–42.PubMed
21.
Errico A, Costanzo V. Mechanisms of replication fork protection: a safeguard for genome stability. Crit Rev Biochem Mol Biol. 2012;47:222–35.CrossRefPubMed
22.
23.
Mailand N, Falck J, Lukas C, Syljuasen RG, Welcker M, Bartek J, Lukas J. Rapid destruction of human Cdc25A in response to DNA damage. Science. 2000;288:1425–9.CrossRefPubMed
24.
Xiao Z, Chen Z, Gunasekera AH, Sowin TJ, Rosenberg SH, Fesik S, Zhang H. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J Biol Chem. 2003;278:21767–73.CrossRefPubMed
25.
Nigg EA. Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol. 2001;2:21–32.CrossRefPubMed
26.
Parker LL, Piwnica-Worms H. Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science. 1992;257:1955–7.CrossRefPubMed
27.
Booher RN, Holman PS, Fattaey A. Human Myt1 is a cell cycle-regulated kinase that inhibits Cdc2 but not Cdk2 activity. J Biol Chem. 1997;272:22300–6.CrossRefPubMed
28.
O’Connell M, Raleigh J, Verkade H, Nurse P. Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation. EMBO J. 1997;16:545–54.CrossRefPubMedPubMedCentral
29.
Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science. 1997;277:1497–501.CrossRefPubMed
30.
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.CrossRef
31.
32.
Vitale I, Galluzzi L, Castedo M, Kroemer G. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat Rev Mol Cell Biol. 2011;12:385–92.CrossRefPubMed
33.
Allday MJ, Inman GJ, Crawford DH, Farrell PJ. DNA damage in human B cells can induce apoptosis, proceeding from G1/S when p53 is transactivation competent and G2/M when it is transactivation defective. EMBO J. 1995;14:4994–5005.PubMedPubMedCentral
34.
Chen T, Stephens PA, Middleton FK, Curtin NJ. Targeting the S and G2 checkpoint to treat cancer. Drug Discov Today. 2012;17:194–202.CrossRefPubMed
35.
Bunch RT, Eastman A. Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor. Clin Cancer Res. 1996;2:791–7.PubMed
36.
Eastman A, Kohn EA, Brown MK, Rathman J, Livingstone M, Blank DH, Gribble GW. A novel indolocarbazole, ICP-1, abrogates DNA damage-induced cell cycle arrest and enhances cytotoxicity: similarities and differences to the cell cycle checkpoint abrogator UCN-01. Mol Cancer Ther. 2002;1:1067–78.PubMed
37.
Lara Jr PN, Mack PC, Synold T, Frankel P, Longmate J, Gumerlock PH, Doroshow JH, Gandara DR. The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid tumors: a California cancer consortium phase I pharmacokinetic and molecular correlative trial. Clin Cancer Res. 2005;11:4444–50.CrossRefPubMed
38.
Perez RP, Lewis LD, Beelen AP, Olszanski AJ, Johnston N, Rhodes CH, Beaulieu B, Ernstoff MS, Eastman A. Modulation of cell cycle progression in human tumors: a pharmacokinetic and tumor molecular pharmacodynamic study of cisplatin plus the Chk1 inhibitor UCN-01 (NSC 638850). Clin Cancer Res. 2006;12:7079–85.CrossRefPubMed
39.
Li T, Christensen SD, Frankel PH, Margolin KA, Agarwala SS, Luu T, Mack PC, Lara Jr PN, Gandara DR. A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial. Invest New Drugs. 2012;30:741–8.CrossRefPubMed
40.
Ma CX, Ellis MJ, Petroni GR, Guo Z, Cai SR, Ryan CE, Craig Lockhart A, Naughton MJ, Pluard TJ, Brenin CM, Picus J, Creekmore AN, Mwandoro T, Yarde ER, Reed J, Ebbert M, Bernard PS, Watson M, Doyle LA, Dancey J, Piwnica-Worms H, Fracasso PM. A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Breast Cancer Res Treat. 2013;137:483–92.CrossRefPubMed
41.
Blasina A, Hallin J, Chen E, Arango ME, Kraynov E, Register J, Grant S, Ninkovic S, Chen P, Nichols T, O'Connor P, Anderes K. Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther. 2008;7:2394–404.CrossRefPubMed
42.
Chilà R, Basana A, Lupi M, Guffanti F, Gaudio E, Rinaldi A, Cascione L, Restelli V, Tarantelli C, Bertoni F, Damia G, Carrassa L. Combined inhibition of Chk1 and Wee1 as a new therapeutic strategy for mantle cell lymphoma. Oncotarget. 2015;6:3394–408.CrossRefPubMed
43.
Matthews DJ, Yakes FM, Chen J, Tadano M, Bornheim L, Clary DO, Tai A, Wagner JM, Miller N, Kim YD, Robertson S, Murray L, Karnitz LM. Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo. Cell Cycle. 2007;6:104–10.CrossRefPubMed
44.
Parsels LA, Morgan MA, Tanska DM, Parsels JD, Palmer BD, Booth RJ, Denny WA, Canman CE, Kraker AJ, Lawrence TS, Maybaum J. Gemcitabine sensitization by checkpoint kinase 1 inhibition correlates with inhibition of a Rad51 DNA damage response in pancreatic cancer cells. Mol Cancer Ther. 2009;8:45–54.CrossRefPubMedPubMedCentral
45.
Syljuåsen RG, Sørensen CS, Nylandsted J, Lukas C, Lukas J, Bartek J. Inhibition of Chk1 by CEP-3891 accelerates mitotic nuclear fragmentation in response to ionizing radiation. Cancer Res. 2004;64:9035–40.CrossRefPubMed
46.
Sausville E, Lorusso P, Carducci M, Carter J, Quinn MF, Malburg L, Azad N, Cosgrove D, Knight R, Barker P, Zabludoff S, Agbo F, Oakes P, Senderowicz A. 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;73:539–49.CrossRefPubMedPubMedCentral
47.
Scagliotti G, Kang JH, Smith D, Rosenberg R, Park K, Kim SW, Su WC, Boyd TE, Richards DA, Novello S, Hynes SM, Myrand SP, Lin J, Smyth EN, Wijayawardana S, Lin AB, Pinder-Schenck M. 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;34:625–35.CrossRefPubMed
48.
Thompson R, Meuth M, Woll P, Zhu Y, Danson S. Treatment with the Chk1 inhibitor Gö6976 enhances cisplatin cytotoxicity in SCLC cells. Int J Oncol. 2012;40:194–202.PubMed
49.
Montano R, Chung I, Garner KM, Parry D, Eastman A. Preclinical development of the novel Chk1 inhibitor SCH900776 in combination with DNA-damaging agents and antimetabolites. Mol Cancer Ther. 2012;11:427–38.CrossRefPubMed
50.
Daud AI, Ashworth MT, Strosberg J, Goldman JW, Mendelson D, Springett G, Venook AP, Loechner S, Rosen LS, Shanahan F, Parry D, Shumway S, Grabowsky JA, Freshwater T, Sorge C, Kang SP, Isaacs R, Munster PN. Phase I dose-escalation trial of checkpoint kinase 1 inhibitor MK-8776 as monotherapy and in combination with gemcitabine in patients with advanced solid tumors. J Clin Oncol. 2015;33:1060–6.CrossRefPubMed
51.
Walton MI, Eve PD, Hayes A, Valenti MR, De Haven Brandon AK, Box G, Hallsworth A, Smith EL, Boxall KJ, Lainchbury M, Matthews TP, Jamin Y, Robinson SP, Aherne GW, Reader JC, Chesler L, Raynaud FI, Eccles SA, Collins I, Garrett MD. CCT244747 is a novel potent and selective CHK1 inhibitor with oral efficacy alone and in combination with genotoxic anticancer drugs. Clin Cancer Res. 2012;18:5650–61.CrossRefPubMedPubMedCentral
52.
Sakurikar N, Eastman A. Will targeting Chk1 have a role in the future of cancer therapy? J Clin Oncol. 2015;33:1075–7.CrossRefPubMed
53.
Karp JE, Thomas BM, Greer JM, Sorge C, Gore SD, Pratz KW, Smith BD, Flatten KS, Peterson K, Schneider P, Mackey K, Freshwater T, Levis MJ, McDevitt MA, Carraway HE, Gladstone DE, Showel MM, Loechner S, Parry DA, Horowitz JA, Isaacs R, Kaufmann SH. Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias. Clin Cancer Res. 2012;18:6723–31.CrossRefPubMedPubMedCentral
54.
Peasland A, Wang LZ, Rowling E, Kyle S, Chen T, Hopkins A, Cliby WA, Sarkaria J, Beale G, Edmondson RJ, Curtin NJ. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer. 2011;105:372–81.CrossRefPubMedPubMedCentral
55.
Hirai H, Iwasawa Y, Okada M, Arai T, Nishibata T, Kobayashi M, Kimura T, Kaneko N, Ohtani J, Yamanaka K, Itadani H, Takahashi-Suzuki I, Fukasawa K, Oki H, Nambu T, Jiang J, Sakai T, Arakawa H, Sakamoto T, Sagara T, Yoshizumi T, Mizuarai S, Kotani H. 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.CrossRefPubMed
56.
Bridges KA, Hirai H, Buser CA, Brooks C, Liu H, Buchholz TA, Molkentine JM, Mason KA, Meyn RE. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011;17:5638–48.CrossRefPubMedPubMedCentral
57.
Hirai H, Arai T, Okada M, Nishibata T, Kobayashi M, Sakai N, Imagaki K, Ohtani J, Sakai T, Yoshizumi T, Mizuarai S, Iwasawa Y, Kotani H. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol Ther. 2010;9:514–22.CrossRefPubMed
58.
Caretti V, Hiddingh L, Lagerweij T, Schellen P, Koken PW, Hulleman E, van Vuurden DG, Vandertop WP, Kaspers GJ, Noske DP, Wurdinger T. WEE1 kinase inhibition enhances the radiation response of diffuse intrinsic pontine gliomas. Mol Cancer Ther. 2013;12:141–50.CrossRefPubMed
59.
Rajeshkumar NV, De Oliveira E, Ottenhof N, Watters J, Brooks D, Demuth T, Shumway SD, Mizuarai S, Hirai H, Maitra A, Hidalgo M. MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. Clin Cancer Res. 2011;17:2799–806.CrossRefPubMedPubMedCentral
60.
61.
Kreahling JM, Gemmer JY, Reed D, Letson D, Bui M, Altiok S. MK1775, a selective Wee1 inhibitor, shows single-agent antitumor activity against sarcoma cells. Mol Cancer Ther. 2012;11:174–82.CrossRefPubMed
62.
Aarts M, Sharpe R, Garcia-Murillas I, Gevensleben H, Hurd MS, Shumway SD, Toniatti C, Ashworth A, Turner NC. Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. Cancer Discov. 2012;2:524–39.CrossRefPubMed
63.
Beck H, Nähse-Kumpf V, Larsen MS, O’Hanlon KA, Patzke S, Holmberg C, Mejlvang J, Groth A, Nielsen O, Syljuåsen RG, Sørensen CS. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption. Mol Cell Biol. 2012;32:4226–36.CrossRefPubMedPubMedCentral
64.
Guertin AD, Li J, Liu Y, Hurd MS, Schuller AG, Long B, Hirsch HA, Feldman I, Benita Y, Toniatti C, Zawel L, Fawell SE, Gilliland DG, Shumway SD. Preclinical evaluation of the WEE1 inhibitor MK-1775 as single-agent anticancer therapy. Mol Cancer Ther. 2013;12:1442–52.CrossRefPubMed
65.
Do K, Wilsker D, Ji J, Zlott J, Freshwater T, Kinders RJ, Collins J, Chen AP, Doroshow JH, Kummar S. Phase I study of single-agent AZD1775 (MK-1775), a Wee1 kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol. 2015;33:3409–15.CrossRefPubMed
66.
Musacchio A, Salmon ED. The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol. 2007;8:379–93.CrossRefPubMed
67.
Sudakin V, Chan GK, Yen TJ. Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol. 2001;154:925–36.CrossRefPubMedPubMedCentral
68.
Zhou J, Giannakakou P. Targeting microtubules for cancer chemotherapy. Curr Med Chem Anticancer Agents. 2005;5:65–71.CrossRefPubMed
69.
Rieder CL, Maiato H. Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev Cell. 2004;7:637–51.CrossRefPubMed
70.
Allan LA, Clarke PR. Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis. Mol Cell. 2007;26:301–10.CrossRefPubMed
71.
Harley ME, Allan LA, Sanderson HS, Clarke PR. Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J. 2010;29:2407–20.CrossRefPubMedPubMedCentral
72.
Sakurikar N, Eichhorn JM, Alford SE, Chambers TC. Identification of a mitotic death signature in cancer cell lines. Cancer Lett. 2014;343:232–8.CrossRefPubMed
73.
Zhou L, Cai X, Han X, Xu N, Chang DC. CDK1 switches mitotic arrest to apoptosis by phosphorylating Bcl-2/Bax family proteins during treatment with microtubule interfering agents. Cell Biol Int. 2014;38:737–46.CrossRefPubMed
74.
Brito DA, Rieder CL. Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr Biol. 2006;16:1194–200.CrossRefPubMedPubMedCentral
75.
Topham CH, Taylor SS. Mitosis and apoptosis: how is the balance set? Curr Opin Cell Biol. 2013;25:780–5.CrossRefPubMed
76.
Gascoigne KE, Taylor SS. How do anti-mitotic drugs kill cancer cells? J Cell Sci. 2009;122:2579–85.CrossRefPubMed
77.
Horwitz SB, Cohen D, Rao S, Ringel I, Shen HJ, Yang CP. Taxol: mechanisms of action and resistance. J Natl Cancer Inst Monogr. 1993;15:55–61.PubMed
78.
Kadoyama K, Kuwahara A, Yamamori M, Brown JB, Sakaeda T, Okuno Y. Hypersensitivity reactions to anticancer agents: data mining of the public version of the FDA adverse event reporting system, AERS. J Exp Clin Cancer Res. 2009;28:130.CrossRef
79.
80.
Mayer TU, Kapoor TM, Haggarty SJ, King RW, Schreiber SL, Mitchison TJ. Small molecule inhibitor of mitotic spindle bipolarity identified in a phenotype-based screen. Science. 1999;286:971–4.CrossRefPubMed
81.
Duhl DM, Renhowe PA. Inhibitors of kinesin motor proteins-research and clinical progress. Curr Opin Drug Discov Devel. 2005;8:431–6.PubMed
82.
El-Nassan HB. Advances in the discovery of kinesin spindle protein (Eg5) inhibitors as antitumor agents. Eur J Med Chem. 2013;62:614–31.CrossRefPubMed
83.
Wang J, Cui F, Wang X, Xue Y, Chen J, Yu Y, Lu H, Zhang M, Tang H, Peng Z. Elevated kinesin family member 26B is a prognostic biomarker and a potential therapeutic target for colorectal cancer. J Exp Clin Cancer Res. 2015;34:13.CrossRefPubMedPubMedCentral
84.
Zhang Y, Liu Y, Yang YX, Xia JH, Zhang HX, Li HB, Yu CZ. The expression of PLK-1 in cervical carcinoma: a possible target for enhancing chemosensitivity. J Exp Clin Cancer Res. 2009;28:130.CrossRefPubMedPubMedCentral
85.
Wu X, Liu W, Cao Q, Chen C, Chen Z, Xu Z, Li W, Liu F, Yao X. Inhibition of Aurora B by CCT137690 sensitizes colorectal cells to radiotherapy. J Exp Clin Cancer Res. 2014;33:13.CrossRefPubMedPubMedCentral
86.
Lens SM, Voest EE, Medema RH. Shared and separate functions of polo-like kinases and aurora kinases in cancer. Nat Rev Cancer. 2010;10:825–41.CrossRefPubMed
87.
Aart M, Linardopoulos S, Turner NC. Tumour selective targeting of cell cycle kinases for cancer treatment. Curr Opin Pharmacol. 2013;13:529–35.CrossRef
88.
Visconti R, Palazzo L, Della Monica R, Grieco D. Fcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit. Nat Commun. 2012;3:894.CrossRefPubMedPubMedCentral
89.
90.
Della Monica R, Visconti R, Cervone N, Serpico AF, Grieco D. Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression. Elife. 2015;4, e10399.CrossRefPubMedPubMedCentral
91.
D’Angiolella V, Mari C, Nocera D, Rametti L, Grieco D. The spindle checkpoint requires cyclin-dependent kinase activity. Genes Dev. 2003;17:2520–5.CrossRefPubMedPubMedCentral
92.
Visconti R, Della Monica R, Palazzo L, D’Alessio F, Raia M, Improta S, Villa MR, Del Vecchio L, Grieco D. The Fcp1-Wee1-Cdk1 axis affects spindle assembly checkpoint robustness and sensitivity to antimicrotubule cancer drugs. Cell Death Differ. 2015;22:1551–60.CrossRefPubMedPubMedCentral
Metadata
Title
Cell cycle checkpoint in cancer: a therapeutically targetable double-edged sword
Authors
Roberta Visconti
Rosa Della Monica
Domenico Grieco
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2016
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-016-0433-9

Other articles of this Issue 1/2016

Journal of Experimental & Clinical Cancer Research 1/2016 Go to the issue

Research

Interleukin-9 promotes cell survival and drug resistance in diffuse large B-cell lymphoma

Research

Inhibition of EZH2 via activation of SAPK/JNK and reduction of p65 and DNMT1 as a novel mechanism in inhibition of human lung cancer cells by polyphyllin I

Research

Non-benzoquinone geldanamycin analogs trigger various forms of death in human breast cancer cells

Research

Antitumor activity of TY-011 against gastric cancer by inhibiting Aurora A, Aurora B and VEGFR2 kinases

Research

EphA1 activation promotes the homing of endothelial progenitor cells to hepatocellular carcinoma for tumor neovascularization through the SDF-1/CXCR4 signaling pathway

Research

Integrated analysis of microRNA regulatory network in nasopharyngeal carcinoma with deep sequencing
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits