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Cell cycle, CDKs and cancer: a changing paradigm
Abstract
Tumour-associated cell cycle defects are often mediated by alterations in cyclin-dependent kinase (CDK) activity. Misregulated CDKs induce unscheduled proliferation as well as genomic and chromosomal instability. According to current models, mammalian CDKs are essential for driving each cell cycle phase, so therapeutic strategies that block CDK activity are unlikely to selectively target tumour cells. However, recent genetic evidence has revealed that, whereas CDK1 is required for the cell cycle, interphase CDKs are only essential for proliferation of specialized cells. Emerging evidence suggests that tumour cells may also require specific interphase CDKs for proliferation. Thus, selective CDK inhibition may provide therapeutic benefit against certain human neoplasias.
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“In contrast, the demonstration that inactivation of these genes can prevent oncogene-induced tumor development in mouse models reinforced the view that these enzymes might be suitable cancer-specific drug targets (65).”
From Targeting CDK4 and CDK6: From Discovery to Therapy (2016) · cites this paper as [65]
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Cites
1 retracted
Fasano, C. A., Dimos, J. T., Ivanova, N. B., Lowry, N. A., Lemischka, I. R., & Temple, S. (2007) · Cell stem cell · doi:10.1016/j.stem.2007.04.001 · Cited by 308
RetractedTargeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Farmer, H., McCabe, N., Lord, C. J., Tutt, A. N. J., Johnson, D. A., Richardson, T. B., Santarosa, M., Dillon, K. J., Hickson, I., Knights, C., et al. (2005) · Nature · doi:10.1038/nature03445 · Cited by 6,683
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,218
Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
p21 is a universal inhibitor of cyclin kinases
Xiong, Y., Hannon, G., Zhang, H., Casso, D., Kobayashi, R., & Beach, D. (1993) · Nature · doi:10.1038/366701a0 · Cited by 3,691
A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4.
Serrano, M., Hannon, G. J., & Beach, D. (1993) · Nature · doi:10.1038/366704a0 · Cited by 3,650
Patterns of somatic mutation in human cancer genomes
Greenman, C. D., Stephens, P., Smith, R., Dalgliesh, G. L., Hunter, C., Bignell, G. R., Davies, H. R., Teague, J. W., Butler, A. P., Stevens, C., et al. (2007) · Nature · doi:10.1038/nature05610 · Cited by 3,143
Kastan, M. B., Zhan, Q., El-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B., & Fornace, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90593-2 · Cited by 3,047
Cell-cycle checkpoints and cancer
Kastan, M. B., & Bartek, J. (2004) · Nature · doi:10.1038/nature03097 · Cited by 2,836
Research works printed but not linked: 1
- Hanks, S. et al. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nature Genet. 36, 1159–1161 (2004). · DOI
Cited by
Sorted by citations
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712
“CDK1, at least in some tissues, may be the crucial target of p21 in tumorigenesi”
BackgroundMonitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay
Molina, D. M., Jafari, R., Ignatushchenko, M., Seki, T., Larsson, E. A., Dan, C., Sreekumar, L., Cao, Y., & Nordlund, P. (2013) · Science · doi:10.1126/science.1233606 · Cited by 2,261
Programmed Cell Death in Animal Development and Disease
Fuchs, Y., & Steller, H. (2011) · Cell · doi:10.1016/j.cell.2011.10.033 · Cited by 1,915
“Other examples include the elimination of cells in response to viral infection, unrepaired DNA damage, cellcycle perturbations, and fate and differentiation defects (Abrams et al., 1993; Rossel and Capecchi, 1999; Derry et al., 2001, Vousden and Prives, 2009; Malumbres and Barbacid, 2009; Koto et al., 2011).”
Finn, R. S., Crown, J. P., Lang, I., Boer, K., Bondarenko, I. M., Kulyk, S. O., Ettl, J., Patel, R., Pinter, T., Schmidt, M., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(14)71159-3 · Cited by 1,900
Cell cycle proteins as promising targets in cancer therapy
Otto, T., & Siciński, P. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2016.138 · Cited by 1,931
“Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint.”
Iron and cancer: more ore to be mined
Torti, S. V., & Torti, F. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3495 · Cited by 1,621
Malumbres, M. (2014) · Genome biology · doi:10.1186/gb4184 · Cited by 1,730
“This simplified view is obscured owing to multiple non-consensus interactions between CDKs and cyclins and compensatory roles [6].”
BackgroundSelf-citationCdks, cyclins and CKIs: roles beyond cell cycle regulation
Lim, S., & Kaldis, P. (2013) · Development · doi:10.1242/dev.091744 · Cited by 1,558
“This increased Cdk complexity is thought to satisfy the requirement for a more elaborate control over the proliferation of different cell types during the advancement from unicellular to complex multicellular organisms (Malumbres and Barbacid, 2009).”
BackgroundMatthews, H. K., Bertoli, C., & de Bruin, R. A. M. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00404-3 · Cited by 1,506
Cyclin D as a therapeutic target in cancer
Musgrove, E. A., Caldon, C. E., Barraclough, J., Stone, A., & Sutherland, R. L. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3090 · Cited by 1,370
“by causing proliferation that is independent of normal extracellular cues, or by over-riding checkpoints that ensure genomic integrity and stabilit”
BackgroundTreating cancer with selective CDK4/6 inhibitors
O'Leary, B., Finn, R. S., & Turner, N. C. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.26 · Cited by 1,137
Emerging roles of E2Fs in cancer: an exit from cell cycle control
Chen, H., Tsai, S., & Leone, G. W. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2696 · Cited by 1,052
Circular RNAs function as ceRNAs to regulate and control human cancer progression
Zhong, Y., Du, Y., Yang, X. F., Mo, Y., Fan, C., Xiong, F., Ren, D., Ye, X., Li, C., Wang, Y., et al. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0827-8 · Cited by 1,002
“circTCF25 proliferation miR-103a-3p / miR-107 CDK6 bladder cancer up [38]”
BackgroundElectrochemical Methods for the Analysis of Clinically Relevant Biomolecules
Labib, M., Sargent, E. H., & Kelley, S. O. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.6b00220 · Cited by 994
Targeting CDK4 and CDK6: From Discovery to Therapy
Sherr, C. J., Beach, D., & Shapiro, G. I. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0894 · Cited by 936
Cell cycle kinases as therapeutic targets for cancer
Lapenna, S., & Giordano, A. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2907 · Cited by 934
“In complex with cyclin A, CDK1 is abruptly activated at the transition from the second gap (G2) phase to the mitosis (M) phase to facilitate the commencement of mitosis through regulation of chromosome condensation and microtubule dynamic”
BackgroundExploiting senescence for the treatment of cancer
Wang, L., Lankhorst, L., & Bernards, R. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-022-00450-9 · Cited by 867
Revisiting the hallmarks of cancer.
Fouad, Y. A., & Aanei, C. M. (2017) · Europe PMC (PubMed Central) · Cited by 875
Targeting oncogenic Myc as a strategy for cancer treatment
Chen, H., Liu, H., & Qing, G. (2018) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-018-0008-7 · Cited by 834
Control of protein stability by post-translational modifications
Lee, J. M., Hammarén, H. M., Savitski, M. M., & Baek, S. H. (2023) · Nature Communications · doi:10.1038/s41467-023-35795-8 · Cited by 896
Sustained proliferation in cancer: Mechanisms and novel therapeutic targets
Feitelson, M. A., Arzumanyan, A. L., Kulathinal, R. J., Blain, S. W., Holcombe, R. F., Mahajna, J. A., Marino, M., Martínez‐Chantar, M. L., Nawroth, R., Sánchez-García, I., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.02.006 · Cited by 818
Patnaik, A., Rosen, L. S., Tolaney, S. M., Tolcher, A. W., Goldman, J. W., Gandhi, L., Papadopoulos, K. P., Beeram, M., Rasco, D. W., Hilton, J. F., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0095 · Cited by 743
Herrera-Abreu, M. T., Palafox, M., Asghar, U. S., Rivas, M. A., Cutts, R. J., García-Murillas, I., Pearson, A., Guzmán, M., Rodríguez, O., Grueso, J., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-0728 · Cited by 781
Dickler, M. N., Tolaney, S. M., Rugo, H. S., Cortés, J., Dieras, V. C., Patt, D. A., Wildiers, H. P. M. W., Hudis, C. A., O’Shaughnessy, J., Zamora, E., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-0754 · Cited by 689
“CDK4 and CDK6, together with D-type cyclins, phosphorylate the Retinoblastoma (Rb) tumor-suppressor protein, leading to release of Rb-bound E2F, which enables progression from the G1 to S phase of the cell cycle (15, 16).”
BackgroundWilliams, G. H., & Stoeber, K. (2011) · The Journal of Pathology · doi:10.1002/path.3022 · Cited by 687
“This releases the brakes on cell cycle progression, and further abrogation of checkpoint control mechanisms leads to the acquisition of genomic instability, which drives tumour evolution [12].”
BackgroundSubtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy
Barretina, J., Taylor, B. S., Banerji, S., Ramos, A. H., Lagos-Quintana, M., DeCarolis, P. L., Shah, K., Socci, N. D., Weir, B. A., Ho, A., et al. (2010) · Nature Genetics · doi:10.1038/ng.619 · Cited by 735
“Furthermore, pharmacological inhibition of CDK4 in dedifferentiated liposarcoma cells with PD0332991, a selective CDK4 and CDK6 inhibitor currently in clinical trial”
Personalized Oncology Through Integrative High-Throughput Sequencing: A Pilot Study
Roychowdhury, S., Iyer, M. K., Robinson, D. R., Lonigro, R. J., Wu, Y.-M., Cao, X., Sundaram, S. K., Sam, L. T., Balbin, O. A., Quist, M. J., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3003161 · Cited by 638
Targetable genetic features of primary testicular and primary central nervous system lymphomas
Chapuy, B., Roemer, M. G. M., Stewart, C., Tan, Y., Abo, R., Zhang, L., Dunford, A. J., Meredith, D. M., Thorner, A. R., Jordanova, E. S., et al. (2015) · Blood · doi:10.1182/blood-2015-10-673236 · Cited by 587
Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration
Mohamed, T., Ang, Y.-S., Radzinsky, E., Zhou, P., Huang, Y., Elfenbein, A., Foley, A., Magnitsky, S. G., & Srivastava, D. (2018) · Cell · doi:10.1016/j.cell.2018.02.014 · Cited by 582
Targeting cell-cycle machinery in cancer
Suski, J. M., Braun, M., Strmiska, V., & Siciński, P. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.03.010 · Cited by 587
Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation
Qi, W., Chan, H., Teng, L., Li, L., Chuai, S., Zhang, R., Zeng, J., Li, M., Fan, H. X., Lin, Y., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1210371110 · Cited by 557
“Qi et al. PNAS | December 26, 2012 | vol. 109 | no. 52 | 21363 CE LL BI O LO G Y D ow nl oa de d at S ha ng ha iT ec h U ni ve rs ity o n M ay 2 2, 2 02 0 EI1 treated cells show specific reduction of H3K27me2 and H3K27me3 (Fig.”
BackgroundMethodInfluentialRetinoids, Retinoic Acid Receptors, and Cancer
Tang, X.-H., & Gudas, L. J. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130303 · Cited by 596
Non-canonical functions of cell cycle cyclins and cyclin-dependent kinases
Hydbring, P., Malumbres, M., & Sicinski, P. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.27 · Cited by 528
Self-citationTargeting Mitosis in Cancer: Emerging Strategies
Dominguez-Brauer, C., Thu, K. L., Mason, J. M., Blaser, H., Bray, M. R., & Mak, T. W. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.11.006 · Cited by 495
“As many excellent reviews on the mammalian cell cycle have been published (Malumbres and Barbacid, 2009; Sherr, 1995; Zhou and Elledge, 2000), we provide here only a brief overview of the process.”
BackgroundSenescent Cells in Cancer Therapy: Friends or Foes?
Wang, B., Kohli, J., & Demaria, M. (2020) · Trends in Cancer · doi:10.1016/j.trecan.2020.05.004 · Cited by 508
“CDK4/6 Inhibitors CDK4 and CDK6 are critical factors for the cell cycle transition from G1 to S phase [52].”
BackgroundCDK4/6 Inhibition in Cancer: Beyond Cell Cycle Arrest
Goel, S., DeCristo, M. J., McAllister, S. S., & Zhao, J. J. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.07.002 · Cited by 506
“In order to enter the cell cycle and commence DNA replication, a cell must pass from the G1 phase into the S phase through a tightly regulated restriction point [7].”
BackgroundRath, O., & Kozielski, F. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3310 · Cited by 514
Targeting CDK4/6 in patients with cancer
Hamilton, E. P., & Infante, J. R. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.03.002 · Cited by 495
“Increased cyclin D-CDK4/6 activity, which promotes phosphorylation of Rb, can occur through several mechanisms, including overexpression of D-type cyclins, mutation or amplification of CDK4/6, or loss of cyclin D-CDK4/6 negative regulators such as p16 [1–3], and ultimately leads to cancer cell growth.”
BackgroundCervical cancer therapies: Current challenges and future perspectives
Burmeister, C. A., Khan, S. F., Schäfer, G., Mbatani, N., Adams, T. S., Moodley, J., & Prince, S. (2022) · Tumour Virus Research · doi:10.1016/j.tvr.2022.200238 · Cited by 534
Braal, C. L., Jongbloed, E. M., Wilting, S. M., Mathijssen, R. H. J., Koolen, S. L. W., & Jager, A. (2020) · Drugs · doi:10.1007/s40265-020-01461-2 · Cited by 462
Advances in sarcoma genomics and new therapeutic targets
Taylor, B. S., Barretina, J., Maki, R. G., Antonescu, C. R., Singer, S., & Ladanyi, M. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3087 · Cited by 444
Kinase inhibition in autoimmunity and inflammation
Zarrin, A. A., Bao, K., Lupardus, P., & Vucic, D. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0082-8 · Cited by 431
An overview of Cdk1-controlled targets and processes
Enserink, J. M., & Kolodner, R. D. (2010) · Cell Division · doi:10.1186/1747-1028-5-11 · Cited by 409
“The fact that aberrant CDK activity underpins proliferation of tumor cells makes it a highly significant research subject [28].”
BackgroundInfluentialPuyol, M., Martín, A., Dubus, P., Mulero, F., Pizcueta, P., Khan, G., Guerra, C., Santamaría, D., & Barbacid, M. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.05.025 · Cited by 415
“Thus, individual interphase Cdks may be specifically required for development of certain tumors depending on the tissue of origin and the driving oncogenic insults (Malumbres and Barbacid, 2009).”
BackgroundInfluentialSelf-citationPosttranscriptional regulation of cancer traits by HuR
Abdelmohsen, K., & Gorospe, M. (2010) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.4 · Cited by 421
Targeting WEE1 Kinase in Cancer
Matheson, C. J., Backos, D. S., & Reigan, P. (2016) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.06.006 · Cited by 412
Casado, P., Rodríguez‐Prados, J., Cosulich, S. C., Guichard, S. M., Vanhaesebroeck, B., Joel, S., & Cutillas, P. R. (2013) · Science Signaling · doi:10.1126/scisignal.2003573 · Cited by 411
Cao, X., Ding, L., Xie, Z., Yang, Y., Whiteman, M., Moore, P. K., & Bian, J. (2018) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7058 · Cited by 412
Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma
Rader, J., Russell, M. R., Hart, L. S., Nakazawa, M. S., Belcastro, L. T., Martinez, D., Li, Y., Carpenter, E. L., Attiyeh, E. F., Diskin, S. J., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1675 · Cited by 394
“This phosphorylation induces the release of RB from E2F transcription factors, and thus enables E2F to transcribe the genes that are required for G1-S phase cell cycle progression and ultimately cellular proliferation (5-7).”
BackgroundMechanisms of Sensitivity and Resistance to CDK4/6 Inhibition
Álvarez‐Fernández, M., & Malumbres, M. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.03.010 · Cited by 399
Self-citationFanconi anaemia and cancer: an intricate relationship
Nalepa, G., & Clapp, D. W. (2018) · Nature reviews. Cancer · doi:10.1038/nrc.2017.116 · Cited by 399
Inhibitors of cyclin-dependent kinases as cancer therapeutics.
Whittaker, S. R., Mallinger, A., Workman, P., & Clarke, P. A. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.008 · Cited by 384
“In any case, RB remains phosphorylated throughout the S, G2 and M phases, and at the end of mitosis it is dephosphorylated by protein phosphatase 1 (Malumbres & Barbacid, 2009).”
Cell cycle on the crossroad of tumorigenesis and cancer therapy
Liu, J., Peng, Y., & Wei, W. (2021) · Trends in Cell Biology · doi:10.1016/j.tcb.2021.07.001 · Cited by 394
Signaling Pathways that Control Cell ProliferationPreprint
Duronio, R. J., & Xiong, Y. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008904 · Cited by 395
“Mouse cells lacking either combination of the three cyclin D proteins or CDK4/6 are more resistant to oncogenic transformation (Sherr and Roberts 2004; Malumbres and Barbacid 2009).”
BackgroundTargeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers
Finn, R. S., Aleshin, A. A., & Slamon, D. J. (2016) · Breast Cancer Research · doi:10.1186/s13058-015-0661-5 · Cited by 385
“Unlike CDKs, cyclins are an extremely diverse family of proteins, subdivided into four classes (A-, B-, D-, E-type cyclins) that act as regulatory subunits of the CDKcyclin holoenzyme [11].”
BackgroundDiril, M. K., Ratnacaram, C. K., Padmakumar, V. C., Du, T., Wasser, M., Coppola, V., Tessarollo, L., & Kaldis, P. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115201109 · Cited by 385
“The mammalian genome contains at least 20 different Cdks, and widespread compensation among Cdks and cyclins has been reported (2, 3).”
BackgroundTargeting cell cycle regulation in cancer therapy
Díaz‐Moralli, S., Tarrado‐Castellarnau, M., Miranda, A., & Cascante, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.01.011 · Cited by 372
Effect of Nanoparticles on the Cell Life Cycle
Mahmoudi, M., Azadmanesh, K., Shokrgozar, M. A., Journeay, W. S., & Laurent, S. (2011) · Chemical Reviews · doi:10.1021/cr1003166 · Cited by 352
Ten things you should know about protein kinases: IUPHAR R eview 14
Fabbro, D., Cowan‐Jacob, S. W., & Möbitz, H. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13096 · Cited by 365
“The physiological activation of kinase occurs in many different ways and their mechanisms of activation have been summarized in excellent reviews (Taylor et al., 2005; Murray, 2007; Rommel et al., 2007; Schmierer and Hill, 2007; Engelman, 2009; Malumbres and Barbacid, 2009; Kawai and Akira, 2010; Lemmon and Schlessing…”
BackgroundTargeting Cyclin-Dependent Kinases in Human Cancers: From Small Molecules to Peptide Inhibitors
Peyressatre, M., Prével, C., Pellerano, M., & Morris, M. C. (2015) · Cancers · doi:10.3390/cancers7010179 · Cited by 358
Nicotine-Mediated Cell Proliferation and Tumor Progression in Smoking-Related Cancers
Schaal, C. M., & Chellappan, S. (2014) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-13-0541 · Cited by 355
“Typically, ATM and ATR protein kinases are activated in response to double- or single-strandedDNA breaks respectively, and they stimulate downstream effectors involved in DNA damage checkpoint response including p53, Chk1, Chk2, and H2AX (62).”
InfluentialThe Requirement for Cyclin D Function in Tumor Maintenance
Choi, Y. J., Li, X., Hydbring, P., Sanda, T., Stefano, J., Christie, A. L., Signoretti, S., Look, A. T., Kung, A. L., von Boehmer, H., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.09.015 · Cited by 342
“CyclinCDK complexes phosphorylate cellular proteins, thereby driving cell cycle progression (Malumbres and Barbacid, 2009).”
BackgroundTherapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer
Quereda, V., Bayle, S., Vena, F., Frydman, S. M., Monastyrskyi, A., Roush, W. R., & Duckett, D. R. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.09.004 · Cited by 352
Targeted protein degradation: advances in drug discovery and clinical practice
Zhong, G., Chang, X., Xie, W., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02004-x · Cited by 326
Michaud, K., Solomon, D. A., Oermann, E. K., Kim, J.-S., Zhong, W.-Z., Prados, M. D., Ozawa, T., James, C. D., & Waldman, T. A. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4559 · Cited by 330
“Deregulation of the cyclin-dependent kinases 4 and 6 (cdk4/6)–cyclin D-INK4—retinoblastoma protein (Rb) signaling pathway is among the most common aberrations found in human cancer (1).”
BackgroundRuiz, S., Panopoulos, A. D., Herrerias, A., Bissig, K., Lutz, M. K., Berggren, W. T., Verma, I. M., & Belmonte, J. C. I. (2010) · Current Biology · doi:10.1016/j.cub.2010.11.049 · Cited by 325
“This phosphorylation is mediated by cyclindependent kinases (CDKs), which require for their activation the binding of cyclins (Cyc) [18].”
BackgroundPrecision medicine for metastatic breast cancer—limitations and solutions
Arnedos, M., Vicier, C., Loi, S., Lefèbvre, C., Michiels, S., Bonnefoi, H. R., & André, F. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.123 · Cited by 322
Cyclin-dependent protein kinases and cell cycle regulation in biology and disease
Pellarin, I., Dall’Acqua, A., Favero, A., Segatto, I., Rossi, V., Crestan, N., Karimbayli, J., Belletti, B., & Baldassarre, G. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02080-z · Cited by 381
Assaying Cell Cycle Status Using Flow Cytometry
Kim, K. H., & Sederstrom, J. M. (2015) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb2806s111 · Cited by 311
Mitotic and mitogenic Wnt signalling
Niehrs, C., & Acebron, S. P. (2012) · The EMBO Journal · doi:10.1038/emboj.2012.124 · Cited by 305
“Cyclin D accumulates and regulates many G1 events (Baldin et al , 1993; Malumbres and Barbacid, 2009), including phosphorylation and inhibition of the Retinoblastoma (Rb) complex, which increases cyclin E levels, whose accumulation acts as G1/S checkpoint (Dulic et al , 1992).”
InfluentialDYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly
Litovchick, L., Florens, L. A., Swanson, S. K., Washburn, M. P., & DeCaprio, J. A. (2011) · Genes & Development · doi:10.1101/gad.2034211 · Cited by 302
“Binding and inhibition of E2Fs by RB family members are relieved by CDK (cyclin-dependent kinase) protein kinases that phosphorylate all RB proteins in a cell cycle-dependent manner (Cobrinik 2005; Malumbres and Barbacid 2009).”
BackgroundRegulation of cell proliferation by hypoxia-inducible factors
Hubbi, M. E., & Semenza, G. L. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00279.2015 · Cited by 311
“CDK2 binds to cyclin E at the G1/S phase transition and to cyclin A at S phase, followed by CDK4 and CDK6, which both bind to cyclin D (66).”
BackgroundZhang, H., Deng, T., Ge, S., Liu, Y., Bai, M., Zhu, K., Fan, Q., Li, J., Ning, T., Tian, F., et al. (2018) · Oncogene · doi:10.1038/s41388-018-0619-z · Cited by 303
RetractedDesigning a broad-spectrum integrative approach for cancer prevention and treatment
Block, K. I., Gyllenhaal, C., Lowe, L. J., Amedei, A., Amin, A. R. M. R., Amin, A., Aquilano, K., Arbiser, J. L., Arreola, A., Arzumanyan, A. L., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.09.007 · Cited by 308
“survival strategies distinguishing CSCs from normal tissue stem cells involve lack of cellular differentiation and alterations in cell metabolism, such as higher antioxidant levels [83,84].”
BackgroundBetulin and betulinic acid: triterpenoids derivatives with a powerful biological potential
Hordyjewska, A., Ostapiuk, A., Horecka, A., & Kurzepa, J. (2019) · Phytochemistry Reviews · doi:10.1007/s11101-019-09623-1 · Cited by 304
Zerdes, I., Matikas, A., Bergh, J. C. S., Rassidakis, G. Z., & Foukakis, T. (2018) · Oncogene · doi:10.1038/s41388-018-0303-3 · Cited by 305
“Cyclin-dependent kinases (CDKs) have a key role in cell cycle [89].”
BackgroundPrognostic relevance of genetic alterations in diffuse lower-grade gliomas
Aoki, K., Nakamura, H., Suzuki, H., Matsuo, K., Kataoka, K., Shimamura, T., Motomura, K., Ohka, F., Shiina, S., Yamamoto, T., et al. (2018) · Neuro-Oncology · doi:10.1093/neuonc/nox132 · Cited by 307
Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition
Johnson, N., Li, Y., Walton, Z. E., Cheng, K. A., Li, D., Rodig, S. J., Moreau, L. A., Unitt, C., Bronson, R. T., Thomas, H. D., et al. (2011) · Nature Medicine · doi:10.1038/nm.2377 · Cited by 293
“2377" language="eng" relation="no"> Cdk1 is a core component of the cell cycle machinery, and forms complexes with cyclins A and B to promote S, G2 and M phase progressio”
Wiśniewski, J. R., Ostasiewicz, P., & Mann, M. (2011) · Journal of Proteome Research · doi:10.1021/pr200019m · Cited by 290
The role of CDC25C in cell cycle regulation and clinical cancer therapy: a systematic review
Liu, K., Zheng, M., Lu, R., Du, J., Zhao, Q., Li, Z., Li, Y., & Zhang, S. (2020) · Cancer Cell International · doi:10.1186/s12935-020-01304-w · Cited by 297
Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update
Tadesse, S., Caldon, C. E., Tilley, W. D., & Wang, S. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01469 · Cited by 285
Cyclin-dependent kinases regulate epigenetic gene silencing through phosphorylation of EZH2
Chen, D., Bohrer, L. R., Rai, A. N., Pan, Y., Gan, L., Zhou, X., Bagchi, A., Simon, J. A., & Huang, H. (2010) · Nature Cell Biology · doi:10.1038/ncb2116 · Cited by 292
“Because CDK activity is often elevated in human cancer”
BackgroundSignaling through cyclin D-dependent kinases
Choi, Y., & Anders, L. (2013) · Oncogene · doi:10.1038/onc.2013.137 · Cited by 289
de Queiroz, E. A. I. F., Puukila, S., Eichler, R. A. D. S., Sampaio, S. C., Forsyth, H. L., Lees, S. J., Barbosa, A. M., Dekker, R. F. H., Fortes, Z. B., & Khaper, N. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098207 · Cited by 291
“Cell cycle arrest in the Sub G1, G0 and G1 phases can lead to apoptosis [24].”
BackgroundCyclin E/CDK2: DNA Replication, Replication Stress and Genomic Instability
Fagundes, R., & Teixeira, L. K. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.774845 · Cited by 289
“Oscillations in Cyclin levels determine fluctuations in CDK activity, which ultimately control cell cycle phase transitions (Malumbres and Barbacid, 2009; Matthews et al., 2021).”
BackgroundThe double dealing of cyclin D1
Tchakarska, G., & Sola, B. (2020) · Cell Cycle · doi:10.1080/15384101.2019.1706903 · Cited by 278
“Diverse heterodimeric complexes form, with D-type cyclins (D1, D2 and D3) associating with CDK4 or CDK6 (CDK4/6, two serine/threonine kinases functionally redundant in most tissues [1]), to control the progression through the G1 phase, the G1-to-S phase transition, thereby initiating DNA replication [2].”
BackgroundMicroRNA dysregulation in gastric cancer: a new player enters the game
Wu, W. K. K., Lee, C., Cho, C. H., Fan, D., Wu, K., Yu, J. Q., & Sung, J. J. �. (2010) · Oncogene · doi:10.1038/onc.2010.352 · Cited by 279
“Cyclin AsCDK2 complex is active during both S and gap 2 (G 2 ) phases, whereas an elevation in cyclin BsCDK1 activity at the late G 2 phase triggers progression to mitosis (M) phase (”
BackgroundTranscriptional role of cyclin D1 in development revealed by a genetic-proteomic screen
Bienvenu, F., Jirawatnotai, S., Elias, J. E., Meyer, C. A., Mizeracka, K., Marson, A., Frampton, G. M., Cole, M. F., Odom, D. T., Odajima, J., et al. (2010) · Nature · doi:10.1038/nature08684 · Cited by 276
Cell-Cycle Proteins Control Production of Neutrophil Extracellular Traps
Amulic, B., Knackstedt, S. L., Abed, U. A., Deigendesch, N., Harbort, C. J., Caffrey, B. E., Brinkmann, V., Heppner, F. L., Hinds, P. W., & Zychlinsky, A. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.10.013 · Cited by 275
“Furthermore, NET formation also requires production of ROS (Fuchs et al., 2007), which can damage DNA and activate the DNA damage checkpoint in both dividing cells (Malumbres and Barbacid, 2009) and in neutrophils (Harbort et al., 2015).”
BackgroundInfluentialFueling the Cell Division Cycle
Salazar‐Roa, M., & Malumbres, M. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.08.009 · Cited by 287
Self-citationPetrarca, C., Clemente, E., Giampaolo, L. D., Mariani‐Costantini, R., Leopold, K., Schindl, R., Lotti, L. V., Mangifesta, R., Sabbioni, E., Niu, Q. L., et al. (2014) · Journal of Immunology Research · doi:10.1155/2014/295092 · Cited by 266
“Studying the influence of potential toxicants on the G1-phase of the cell cycle is of central importance; in fact, most, if not all, human cancer types show a deregulated control of G1 progression, a period in which cells decide whether to start proliferation or stay quiescent [31, 32].”
BackgroundIntegrating Old and New Paradigms of G1/S Control
Rubin, S. M., Sage, J., & Skotheim, J. M. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.08.020 · Cited by 283
“Rather than existing in a continuum of phosphorylation states, which results from progressive and successive phosphorylation by the G1 Cdks, Rb is present in discrete states.”
InfluentialStructural insights into the functional diversity of the CDK–cyclin family
Wood, D. J., & Endicott, J. (2018) · Open Biology · doi:10.1098/rsob.180112 · Cited by 272
Targeting signaling pathways in prostate cancer: mechanisms and clinical trials
He, Y., Xu, W., Xiao, Y., Huang, H., Gu, D., & Ren, S. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01042-7 · Cited by 287
“The cyclin D-CDK4/6 complexes subsequently phosphorylate and inactivate the retinoblastoma (RB) tumor suppressor protein.(353,354) RB proteins typically bind to the transcription factor E2Fs, such as E2F1, to limit the expression of many E2F target genes that are involved in the cell cycle and mitotic progression.”
BackgroundCianfanelli, V., Fuoco, C., Lorente, M., Salazar‐Roa, M., Quondamatteo, F., Gherardini, P. F., Zio, D. D., Nazio, F., Antonioli, M., D’Orazio, M., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3072 · Cited by 267
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283
Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy
Roberts, P. J., Bisi, J. E., Strum, J. C., Combest, A. J., Darr, D. B., Usary, J. E., Zamboni, W. C., Wong, K.-K., Perou, C. M., & Sharpless, N. E. (2012) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djs002 · Cited by 255
“There are four proliferative CDKs: CDK1, which predominantly regulates the transition from G2 to M phase, and CDK2/4/6, which regulate the transition from G1 to S phase (1,2).”
BackgroundMethodCell cycle transcription control: DREAM/MuvB and RB-E2F complexes.
Fischer, M., & Müller, G. A. (2017) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2017.1360836 · Cited by 255
“Pathways leading to the formation of pocket protein repressor complexes are altered in many cancer types ( Sherr and DePinho 2000, Sherr and McCormick 2002, Malumbres and Barbacid 2009) and are promising targets for cancer therapeutics (O’Leary et al. 2016).”
BackgroundUbiquitin Ligases and Cell Cycle Control
Teixeira, L. K., & Reed, S. I. (2013) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060410-105307 · Cited by 262
WEE1 Kinase Targeting Combined with DNA-Damaging Cancer Therapy Catalyzes Mitotic Catastrophe
Hamer, P. C. D. W., Mir, S. E., Noske, D. P., Noorden, C. J. F. V., & Würdinger, T. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2537 · Cited by 254
“kinase out of 14 that is indispensable and that alone can drive the cell cycle (1, 2).”
Background
Metadata
- Authors
- Malumbres, M., & Barbacid, M.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Venue
- Nature Reviews Cancer
- Published
- 2009-03
- Volume
- 9
- Issue
- 3
- Pages
- 153-166
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2046024621
- Cited by
- 3,957
- References
- 178
- Citations by year
- 2026: 191 · 2025: 241 · 2024: 266 · 2023: 277 · 2022: 297 · 2021: 318 · 2020: 272 · 2019: 222 · 2018: 237 · 2017: 260 · 2016: 195 · 2015: 228 · 2014: 218 · 2013: 206 · 2012: 186
- FWCI
- 15.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- cyclin-dependent kinases, CDK1, cell cycle, tumor cell proliferation, genomic instability, chromosomal instability, cyclin-dependent kinase inhibitors, selective cancer therapy
- MeSH terms
- Animals, Cell Cycle, Chromosome Aberrations, DNA Damage, Humans, Mitosis, Neoplasms, Neoplastic Stem Cells, Cyclins, Cyclin-Dependent Kinases, Cyclin E, Chromosomal Instability, Protein Kinase Inhibitors, Cell Proliferation, Cyclin D
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