Abstract
Colorectal cancer (CRC), one of the most common malignancies worldwide, is often diagnosed
at an advanced stage, and resistance to chemotherapeutic and existing targeted therapy
is a major obstacle to its successful treatment. New targets that offer alternative
clinical options are therefore urgently needed. Recently, perturbation of the spindle
assembly checkpoint (SAC), the surveillance mechanism that maintains anaphase inhibition
until all chromosomes reach the metaphase plate, has been regarded as a promising
target to fight cancer cells, either alone or in combination regimens. Consistent
with this strategy, many cancers, including CRC, exhibit altered expression of SAC
genes. In this article, we review our current knowledge on SAC activity status in
CRC, and on current anti-CRC strategies and future therapeutic perspectives on the
basis of SAC targeting experiments in vitro and in animal models.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Colorectal CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Adjuvant treatment of colon cancer: past, present and future.J Chemother. 2007; 19: 115-122
- Surgical adjuvant therapy for colorectal cancer: current approaches and future directions.Ann Surg Oncol. 2006; 13: 1021-1034
- Assessment of the mitotic spindle assembly checkpoint (SAC) as the target of anticancer therapies.Curr Cancer Drug Targets. 2009; 9: 131-141
- Monitoring the fidelity of mitotic chromosome segregation by the spindle assembly checkpoint.Cell Prolif. 2011; 44: 391-400
- Spindle assembly checkpoint, aneuploidy and tumorigenesis.Cell Cycle. 2009; 8: 3440
International Agency for Research on Cancer. GLOBOCAN 2012. Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available at: http://globocan.iarc.fr. Accessed: May 5, 2015.
- Molecular genetics of colorectal cancer.Ann Gastroenterol. 2014; 27: 9-14
- Familial adenomatous polyposis.Orphanet J Rare Dis. 2009; 4: 22
- Hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome.Dtsch Arztebl Int. 2013; 110: 32-38
- The hallmarks of cancer.Cell. 2000; 100: 57-70
- A genetic model for colorectal tumorigenesis.Cell. 1990; 61: 759-767
- Molecular genetics of colorectal cancer.Annu Rev Pathol. 2011; 6: 479-507
- Expression and genomic profiling of colorectal cancer.Biochim Biophys Acta. 2007; 1775: 103-137
- PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival.PLoS One. 2013; 8: e65479
- The chromosomal instability pathway in colon cancer.Gastroenterology. 2010; 138: 2059-2072
- Molecular pathways in colorectal cancer.J Gastroenterol Hepatol. 2012; 27: 1423-1431
- Colorectal cancer carcinogenesis: a review of mechanisms.Cancer Biol Med. 2016; 13: 120-135
- Biomarkers in colorectal cancer.Anticancer Res. 2016; 36: 1093-1102
- Chromosome segregation and cancer: cutting through the mystery.Nat Rev Cancer. 2001; 1: 109-117
- Genetic alterations in colorectal cancer.Gastrointest Cancer Res. 2012; 5: 19-27
- Characterization of sporadic colon cancer by patterns of genomic instability.Cancer Res. 2003; 63: 1608-1614
- Epigenetic changes (aberrant DNA methylation) in colorectal neoplasia.Gut Liver. 2007; 1: 1-11
- Management of colorectal cancer.F1000Prime Rep. 2014; 6: 108
- Targeted therapy in advanced metastatic colorectal cancer: current concepts and perspectives.World J Gastroenterol. 2014; 20: 6102-6112
- Recent therapeutic advances in the treatment of colorectal cancer.Annu Rev Med. 2015; 66: 83-95
- Metastatic colorectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann Oncol. 2014; 25: iii1-iii9
- The spindle-assembly checkpoint in space and time.Nat Rev Mol Cell Biol. 2007; 8: 379-393
- The molecular biology of spindle assembly checkpoint signaling dynamics.Curr Biol. 2015; 25: R1002-R1018
- The kinetochore.Cold Spring Harb Perspect Biol. 2014; 6: a015826
- Studying kinetochore kinases.Methods Mol Biol. 2016; 1413: 333-347
- Kinetochore-microtubule interactions “in check” by Bub1, Bub3 and BubR1: the dual task of attaching and signalling.Cell Cycle. 2008; 7: 1763-1768
- 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: 925-936
- The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint.Curr Biol. 2005; 15: 214-225
- Structural activation of Mad2 in the mitotic spindle checkpoint: the two-state Mad2 model versus the Mad2 template model.J Cell Biol. 2006; 173: 153-157
- Protein metamorphosis: the two-state behavior of Mad2.Structure. 2008; 16: 1616-1625
- Probing the in vivo function of Mad1:C-Mad2 in the spindle assembly checkpoint.EMBO J. 2011; 30: 3322-3336
- The Mad2 partial unfolding model: regulating mitosis through Mad2 conformational switching.J Cell Biol. 2008; 183: 761-768
- Spindle assembly checkpoint silencing and beyond.Cell Cycle. 2016; : 1-2
- Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation.Nature. 2007; 446: 921-925
- Dynein-dependent transport of spindle assembly checkpoint proteins off kinetochores toward spindle poles.FEBS Lett. 2014; 588: 3265-3273
- Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression.J Cell Sci. 2004; 117: 1577-1589
- Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint.Cell. 2001; 106: 83-93
- Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint.Mol Cell. 2004; 16: 387-397
- Multifaceted polo-like kinases: drug targets and antitargets for cancer therapy.Nat Rev Drug Discov. 2010; 9: 643-660
- The family of polo-like kinases.Prog Cell Cycle Res. 1996; 2: 107-114
- Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes.J Cell Biol. 1996; 135: 1701-1713
- Sensing centromere tension: Aurora B and the regulation of kinetochore function.Trends Cell Biol. 2011; 21: 133-140
- The chromosomal passenger complex: one for all and all for one.Cell. 2007; 131: 230-231
- Genetic instability in colorectal cancers.Nature. 1997; 386: 623-627
- Lethality to human cancer cells through massive chromosome loss by inhibition of the mitotic checkpoint.Proc Natl Acad Sci U S A. 2004; 101: 8699-8704
- Mutations of mitotic checkpoint genes in human cancers.Nature. 1998; 392: 300-303
- Genetic and epigenetic inactivation of mitotic checkpoint genes hBUB1 and hBUBR1 and their relationship to survival.Cancer Res. 2002; 62: 13-17
- APC inactivation associates with abnormal mitosis completion and concomitant BUB1B/MAD2L1 up-regulation.Gastroenterology. 2007; 132: 2448-2458
- Reduced level of the spindle checkpoint protein BUB1B is associated with aneuploidy in colorectal cancers.Cell Prolif. 2008; 41: 645-659
- Aberrations of BUBR1 and TP53 gene mutually associated with chromosomal instability in human colorectal cancer.Anticancer Res. 2014; 34: 5421-5427
- Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are risk factors for colorectal cancer.Gastroenterology. 2013; 145: 544-547
- Up-regulation of the mitotic checkpoint component Mad1 causes chromosomal instability and resistance to microtubule poisons.Proc Natl Acad Sci U S A. 2012; 109: E2205-E2214
- Mad2 and p53 expression profiles in colorectal cancer and its clinical significance.World J Gastroenterol. 2003; 9: 1972-1975
- Mad2 and p27 expression profiles in colorectal cancer and its clinical significance.World J Gastroenterol. 2004; 10: 3218-3220
- Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression.Int J Colorectal Dis. 2005; 20: 391-402
- Expression of the mitotic checkpoint gene MAD2L2 has prognostic significance in colon cancer.Int J Cancer. 2007; 120: 207-211
- Overexpression of Mps1 in colon cancer cells attenuates the spindle assembly checkpoint and increases aneuploidy.Biochem Biophys Res Commun. 2014; 450: 1690-1695
- Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability.Cancer Cell. 2003; 4: 483-497
- CDC20 overexpression predicts a poor prognosis for patients with colorectal cancer.J Transl Med. 2013; 11: 142
- Multinuclearity and increased ploidy caused by overexpression of the aurora- and Ipl1-like midbody-associated protein mitotic kinase in human cancer cells.Cancer Res. 1998; 58: 4811-4816
- Mitotic kinase expression and colorectal cancer progression.J Natl Cancer Inst. 1999; 91: 1160-1162
- Pharmacogenetic profiling of Aurora kinase B is associated with overall survival in metastatic colorectal cancer.Pharmacogenomics J. 2011; 11: 93-99
- Nuclear Aurora B and cytoplasmic Survivin expression is involved in lymph node metastasis of colorectal cancer.Oncol Lett. 2012; 3: 1109-1114
- Polo-like kinase 1 is overexpressed in colorectal cancer and participates in the migration and invasion of colorectal cancer cells.Med Sci Monit. 2012; 18: Br237-Br246
- Polo-like kinase 1 expression is a prognostic factor in human colon cancer.World J Gastroenterol. 2005; 11: 5644-5650
- Polo-like kinase 1 (PLK1) is overexpressed in primary colorectal cancers.Cancer Sci. 2003; 94: 148-152
- Comparative expression of the mitotic regulators SAK and PLK in colorectal cancer.Ann Surg Oncol. 2001; 8: 729-740
- Gene expression differences between the microsatellite instability (MIN) and chromosomal instability (CIN) phenotypes in colorectal cancer revealed by high-density cDNA array hybridization.Oncogene. 2002; 21: 3253-3257
- Proliferation state and polo-like kinase1 dependence of tumorigenic colon cancer cells.Stem Cells. 2012; 30: 1819-1830
- Expression of the microtubule-associated protein MAP9/ASAP and its partners AURKA and PLK1 in colorectal and breast cancers.Dis Markers. 2014; 2014: 798170
- Spindle proteins Aurora A and BUB1B, but not Mad2, are aberrantly expressed in dysplastic mucosa of patients with longstanding ulcerative colitis.J Clin Pathol. 2007; 60: 1403-1408
- Multiple putative oncogenes at the chromosome 20q amplicon contribute to colorectal adenoma to carcinoma progression.Gut. 2009; 58: 79-89
- High frequency of TTK mutations in microsatellite-unstable colorectal cancer and evaluation of their effect on spindle assembly checkpoint.Carcinogenesis. 2011; 32: 305-311
- The Aurora kinase family in cell division and cancer.Biochim Biophys Acta. 2008; 1786: 60-72
- Plk1 and Mps1 cooperatively regulate the spindle assembly checkpoint in human cells.Cell Rep. 2015; 12: 66-78
- Polo-like kinase 1 as predictive marker and therapeutic target for radiotherapy in rectal cancer.Am J Pathol. 2010; 177: 918-929
- DNA damage-induced expression of p53 suppresses mitotic checkpoint kinase hMps1: the lack of this suppression in p53MUT cells contributes to apoptosis.J Biol Chem. 2006; 281: 8675-8685
- A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53.Proc Natl Acad Sci U S A. 2009; 106: 3964-3969
- Therapeutic targeting of the mitotic spindle checkpoint through nanoparticle-mediated siRNA delivery inhibits tumor growth in vivo.Cancer Lett. 2011; 304: 128-136
- AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis.Clin Cancer Res. 2007; 13: 3682-3688
- Aurora B kinase inhibitor AZD1152: determinants of action and ability to enhance chemotherapeutics effectiveness in pancreatic and colon cancer.Br J Cancer. 2011; 104: 769-780
- Imaging colon cancer response following treatment with AZD1152: a preclinical analysis of 18Ffluoro-2-deoxyglucose and 3'-deoxy-3'-18Ffluorothymidine imaging.Clin Cancer Res. 2011; 17: 1099-1110
- VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo.Nat Med. 2004; 10: 262-267
- Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors.Cancer Chemother Pharmacol. 2011; 67: 305-314
- Discovery of a potent and selective aurora kinase inhibitor.Bioorg Med Chem Lett. 2008; 18: 4880-4884
- PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity.Clin Cancer Res. 2006; 12: 4080-4089
- Preclinical evaluation of AMG 900, a novel potent and highly selective pan-aurora kinase inhibitor with activity in taxane-resistant tumor cell lines.Cancer Res. 2010; 70: 9846-9854
- Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors.J Med Chem. 2010; 53: 4367-4378
- Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity.J Med Chem. 2009; 52: 379-388
- Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity.Mol Cancer Ther. 2007; 6: 3147-3157
- Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours.Eur J Cancer. 2011; 47: 2256-2264
- PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy.Mol Cancer Ther. 2010; 9: 883-894
- Biological characterization of TAK-901, an investigational, novel, multitargeted Aurora B kinase inhibitor.Mol Cancer Ther. 2013; 12: 460-470
- GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models.Mol Cancer Ther. 2009; 8: 1808-1817
- Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase.J Med Chem. 2010; 53: 3973-4001
- The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN-amplified neuroblastoma in vivo.Mol Cancer Ther. 2011; 10: 2115-2123
- A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors.Clin Cancer Res. 2009; 15: 6694-6701
- Phase I pharmacokinetic and pharmacodynamic study of the aurora kinase inhibitor danusertib in patients with advanced or metastatic solid tumors.J Clin Oncol. 2009; 27: 5094-5101
- PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer.Mol Cancer Ther. 2007; 6: 3158-3168
- A pentacyclic aurora kinase inhibitor (AKI-001) with high in vivo potency and oral bioavailability.J Med Chem. 2008; 51: 4465-4475
- Targeting the mitotic checkpoint to kill tumor cells.Horm Cancer. 2011; 2: 113-116
- Targeting the mitotic checkpoint for cancer therapy with NMS-P715, an inhibitor of MPS1 kinase.Cancer Res. 2010; 70: 10255-10264
- Small-molecule kinase inhibitors provide insight into Mps1 cell cycle function.Nat Chem Biol. 2010; 6: 359-368
- Characterization of the cellular and antitumor effects of MPI-0479605, a small-molecule inhibitor of the mitotic kinase Mps1.Mol Cancer Ther. 2011; 10: 2267-2275
- Selective killing of p53-deficient cancer cells by SP600125.EMBO Mol Med. 2012; 4: 500-514
- Preferential killing of p53-deficient cancer cells by reversine.Cell Cycle. 2012; 11: 2149-2158
- Efficient inhibition of human colorectal carcinoma growth by RNA interference targeting polo-like kinase 1 in vitro and in vivo.Cancer Biother Radiopharm. 2011; 26: 427-436
- Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice.J Clin Invest. 2009; 119: 661-673
- Distinct concentration-dependent effects of the polo-like kinase 1-specific inhibitor GSK461364A, including differential effect on apoptosis.Cancer Res. 2009; 69: 6969-6977
- BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo.Curr Biol. 2007; 17: 316-322
- BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity.Clin Cancer Res. 2009; 15: 3094-3102
- TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens.Mol Cancer Ther. 2012; 11: 700-709
- Discovery of a potent and orally bioavailable benzolactam-derived inhibitor of Polo-like kinase 1 (MLN0905).J Med Chem. 2012; 55: 197-208
- Dissecting the phenotypes of Plk1 inhibition in cancer cells using novel kinase inhibitory chemical CBB2001.Lab Invest. 2012; 92: 1503-1514
- NMS-P937, an orally available, specific small-molecule polo-like kinase 1 inhibitor with antitumor activity in solid and hematologic malignancies.Mol Cancer Ther. 2012; 11: 1006-1016
- In vivo antitumor activity of a novel sulfonamide, HMN-214, against human tumor xenografts in mice and the spectrum of cytotoxicity of its active metabolite, HMN-176.Invest New Drugs. 2003; 21: 387-399
- Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis.Mol Biol Cell. 2007; 18: 4024-4036
- ON01910, a non-ATP-competitive small molecule inhibitor of Plk1, is a potent anticancer agent.Cancer Cell. 2005; 7: 275-286
- Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies.Clin Cancer Res. 2011; 17: 3420-3430
- A phase I pharmacokinetic study of HMN-214, a novel oral stilbene derivative with polo-like kinase-1-interacting properties, in patients with advanced solid tumors.Clin Cancer Res. 2006; 12: 5182-5189
- Phase I study of ON 01910.Na, a novel modulator of the Polo-like kinase 1 pathway, in adult patients with solid tumors.J Clin Oncol. 2008; 26: 5504-5510
- Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years.World J Gastroenterol. 2014; 20: 9775-9827
- Prediction of efficacy and side effects of chemotherapy in colorectal cancer.Recent Results Cancer Res. 2007; 176: 81-88
- Therapeutic antibodies in cancer therapy.Adv Exp Med Biol. 2016; 917: 95-120
- Targeting polo-like kinases: a promising therapeutic approach for cancer treatment.Transl Oncol. 2015; 8: 185-195
- Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer.Am J Cancer Res. 2013; 3: 323-338
Article info
Publication history
Published online: June 23, 2016
Accepted:
June 10,
2016
Received in revised form:
June 3,
2016
Received:
February 15,
2016
Footnotes
V.D., J.T., and P.M.A.S. contributed equally to this work.
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
