Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
March-2018 Volume 39 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2018 Volume 39 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review)

  • Authors:
    • Minghui Liu
    • Hongyu Liu
    • Jun Chen
  • View Affiliations / Copyright

    Affiliations: Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Heping, Tianjin 300052, P.R. China, Tianjin key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Heping, Tianjin 300052, P.R. China
  • Pages: 901-911
    |
    Published online on: January 19, 2018
       https://doi.org/10.3892/or.2018.6221
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

An uncontrolled cell cycle is an obvious marker of tumor cells. The G1‑S phase is an important restriction point in the normal cell cycle, but in cancer cells the restriction function is reduced, leading to uncontrolled cell proliferation. Two cyclin‑dependent kinases (CDKs), CDK4 and CDK6, play a crucial role in the G1‑S phase transition. Inhibitors of CDK4/6 are presently the subjects of numerous studies, and PD 0332991, an inhibitor of CDK4/6, has been used to treat hormone receptor (HR)‑positive, advanced‑stage breast cancer. This inhibitor has also been studied in other cancers, such as lung cancer. In this review, we will discuss the regulation of the normal cell cycle transition from G1 to S phase, the most promising inhibitor of CDK4/6, PD 0332991, as applied in different cancers, and finally we propose a mechanism of acquired resistance as well as the incredible potential for CDK4/6 inhibitors in the treatment of cancer. Briefly, we assert that, going forward, a new treatment pattern for cancer may be a combination therapy with a cell cycle inhibitor and a molecular targeted drug.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Minton K: Cancer immunotherapy: Cell cycle inhibitors boost tumour immunogenicity. Nat Rev Drug Dis. 16:6792017. View Article : Google Scholar

2 

Hamilton E and Infante JR: Targeting CDK4/6 in patients with cancer. Cancer Treat Rev. 45:129–138. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Zhou J, Zhang S, Chen X, Zheng X, Yao Y, Lu G and Zhou J: Palbociclib, a selective CDK4/6 inhibitor, enhances the effect of selumetinib in RAS-driven non-small cell lung cancer. Cancer Lett. 408:130–137. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Bilgin B, Sendur MA, Şener Dede D, Akıncı MB and Yalçın B: A current and comprehensive review of cyclin-dependent kinase ınhibitors for the treatment of metastatic breast cancer. Curr Med Res Opin. 33:1559–1569. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Chen L and Pan J: Dual cyclin-dependent kinase 4/6 inhibition by PD-0332991 induces apoptosis and senescence in oesophageal squamous cell carcinoma cells. Br J Pharmacol. 174:2427–2443. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Patel P, Asbach B, Shteyn E, Gomez C, Coltoff A, Bhuyan S, Tyner AL, Wagner R and Blain SW: Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4. Mol Cell Biol. 35:1506–1522. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Malumbres M, Harlow E, Hunt T, Hunter T, Lahti JM, Manning G, Morgan DO, Tsai LH and Wolgemuth DJ: Cyclin-dependent kinases: A family portrait. Nat Cell Biol. 11:1275–1276. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Malumbres M: Cyclin-dependent kinases. Genome Biology. 15:1222014. View Article : Google Scholar : PubMed/NCBI

9 

Ubersax JA, Woodbury EL, Quang PN, Paraz M, Blethrow JD, Shah K, Shokat KM and Morgan DO: Targets of the cyclin-dependent kinase Cdk1. Nature. 425:859–864. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Baker SJ and Reddy EP: CDK4: A key player in the cell cycle, development, and cancer. Genes Cancer. 3:658–669. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Shah K and Lahiri DK: Cdk5 activity in the brain-multiple paths of regulation. J Cell Sci. 127:2391–2400. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Pinhero R and Yankulov K: Expression and purification of recombinant CDKs: CDK7, CDK8, and CDK9. Methods Mol Biol. 1336:13–28. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Galbraith MD, Donner AJ and Espinosa JM: CDK8: A positive regulator of transcription. Transcription. 1:4–12. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Krystof V, Baumli S and Fürst R: Perspective of cyclin-dependent kinase 9 (CDK9) as a drug target. Curr Pharm Des. 18:2883–2890. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Hu D, Mayeda A, Trembley JH, Lahti JM and Kidd VJ: CDK11 complexes promote pre-mRNA splicing. J Biol Chem. 278:8623–8629. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Chi Y, Huang S, Peng H, Liu M, Zhao J, Shao Z and Wu J: Critical role of CDK11(p58) in human breast cancer growth and angiogenesis. BMC Cancer. 15:7012015. View Article : Google Scholar : PubMed/NCBI

17 

Bajić VP, Su B, Lee HG, Kudo W, Siedlak SL, Zivković L, Spremo-Potparević B, Djelic N, Milicevic Z, Singh AK, et al: Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease. Cell Mol Biol Lett. 16:359–372. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Zhou Y, Han C, Li D, Yu Z, Li F, Li F, An Q, Bai H, Zhang X, Duan Z and Kan Q: Cyclin-dependent kinase 11(p110) (CDK11(p110)) is crucial for human breast cancer cell proliferation and growth. Sci Rep. 5:104332015. View Article : Google Scholar : PubMed/NCBI

19 

Malumbres M and Barbacid M: Mammalian cyclin-dependent kinases. Trends Biochem Sci. 30:630–641. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Shapiro GI: Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 24:1770–1783. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Sakurikar N and Eastman A: Critical reanalysis of the methods that discriminate the activity of CDK2 from CDK1. Cell Cycle. 15:1184–1188. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Sherr CJ: G1 phase progression: Cycling on cue. Cell. 79:551–555. 1994. View Article : Google Scholar : PubMed/NCBI

23 

Li Y, Zhang J, Gao W, Zhang L, Pan Y, Zhang S and Wang Y: Insights on structural characteristics and ligand binding mechanisms of CDK2. Int J Mol Sci. 16:9314–9340. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Flores O, Wang Z, Knudsen KE and Burnstein KL: Nuclear targeting of cyclin-dependent kinase 2 reveals essential roles of cyclin-dependent kinase 2 localization and cyclin E in vitamin D-mediated growth inhibition. Endocrinology. 151:896–908. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Ali S, Heathcote DA, Kroll SH, Jogalekar AS, Scheiper B, Pate H, Brackow J, Siwicka A, Fuchter MJ, Periyasamy M, et al: The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity. Cancer Res. 69:6208–6215. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Kawana H, Tamaru J, Tanaka T, Hirai A, Saito Y, Kitagawa M, Mikata A, Harigaya K and Kuriyama T: Role of p27Kip1 and cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer. Am J Pathol. 153:505–513. 1998. View Article : Google Scholar : PubMed/NCBI

27 

Morgan DO: Cyclin-dependent kinases: Engines, clocks, and microprocessors. Annu Rev Cell Dev Biol. 13:261–291. 1997. View Article : Google Scholar : PubMed/NCBI

28 

Clark AS, Karasic TB, DeMichele A, Vaughn DJ, O'Hara M, Perini R, Zhang P, Lal P, Feldman M, Gallagher M and O'Dwyer PJ: Palbociclib (PD0332991) - a selective and potent cyclin-dependent kinase inhibitor: A review of pharmacodynamics and clinical development. JAMA Oncol. 2:253–260. 2016. View Article : Google Scholar : PubMed/NCBI

29 

Dean JL, McClendon AK and Knudsen ES: Modification of the DNA damage response by therapeutic CDK4/6 inhibition. J Biol Chem. 287:29075–29087. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, Li Y, Carpenter EL, Attiyeh EF, Diskin SJ, et al: Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 19:6173–6182. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Lee Y, Dominy JE, Choi YJ, Jurczak M, Tolliday N, Camporez JP, Chim H, Lim JH, Ruan HB, Yang X, et al: Cyclin D1-Cdk4 controls glucose metabolism independently of cell cycle progression. Nature. 510:547–551. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Weijts BGMW, Westendorp B, Hien BT, Martínez-López LM, Zijp M, Thurlings I, Thomas RE, Schulte-Merker S, Bakker WJ and de Bruin A: Atypical E2Fs inhibit tumor angiogenesis. Oncogene. Sep 18–2017.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

33 

Wirt SE and Sage J: p107 in the public eye: An Rb under study and more. Cell Div. 5:92010. View Article : Google Scholar : PubMed/NCBI

34 

Sadasivam S and DeCaprio JA: The DREAM complex: Master coordinator of cell cycle-dependent gene expression. Nat Rev Cancer. 13:585–595. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Lee MH, Williams BO, Mulligan G, Mukai S, Bronson RT, Dyson N, Harlow E and Jacks T: Targeted disruption of p107: Functional overlap between p107 and Rb. Genes Dev. 10:1621–1632. 1996. View Article : Google Scholar : PubMed/NCBI

36 

Cobrinik D, Lee MH, Hannon G, Mulligan G, Bronson RT, Dyson N, Harlow E, Beach D, Weinberg RA and Jacks T: Shared role of the pRB-related p130 and p107 proteins in limb development. Genes Dev. 10:1633–1644. 1996. View Article : Google Scholar : PubMed/NCBI

37 

Shen Y, Nar R, Fan AX, Aryan M, Hossain MA, Gurumurthy A, Wassel PC, Tang M, Lu J, Strouboulis J and Bungert J: Functional interrelationship between TFII-I and E2F transcription factors at specific cell cycle gene loci. J Cell Biochem. 119:712–722. 2018. View Article : Google Scholar : PubMed/NCBI

38 

Kent LN, Bae S, Tsai SY, Tang X, Srivastava A, Koivisto C, Martin CK, Ridolfi E, Miller GC, Zorko SM, et al: Dosage-dependent copy number gains in E2f1 and E2f3 drive hepatocellular carcinoma. J Clin Invest. 127:830–842. 2017. View Article : Google Scholar : PubMed/NCBI

39 

Conklin JF and Sage J: Keeping an eye on retinoblastoma control of human embryonic stem cells. J Cell Biochem. 108:1023–1030. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Dyson N: The regulation of E2F by pRB-family proteins. Genes Dev. 12:2245–2262. 1998. View Article : Google Scholar : PubMed/NCBI

41 

Lukas J, Petersen BO, Holm K, Bartek J and Helin K: Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression. Mol Cell Biol. 16:1047–1057. 1996. View Article : Google Scholar : PubMed/NCBI

42 

Asano M, Nevins JR and Wharton RP: Ectopic E2F expression induces S phase and apoptosis in Drosophila imaginal discs. Genes Dev. 10:1422–1432. 1996. View Article : Google Scholar : PubMed/NCBI

43 

DeGregori J, Leone G, Ohtani K, Miron A and Nevins JR: E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity. Genes Dev. 9:2873–2887. 1995. View Article : Google Scholar : PubMed/NCBI

44 

Allen KE, La Luna de S, Kerkhoven RM, Bernards R and La Thangue NB: Distinct mechanisms of nuclear accumulation regulate the functional consequence of E2F transcription factors. J Cell Sci. 110:2819–2831. 1997.PubMed/NCBI

45 

Müller H, Moroni MC, Vigo E, Petersen BO, Bartek J and Helin K: Induction of S-phase entry by E2F transcription factors depends on their nuclear localization. Mol Cell Biol. 17:5508–5520. 1997. View Article : Google Scholar : PubMed/NCBI

46 

Wu Z, Zheng S and Yu Q: The E2F family and the role of E2F1 in apoptosis. Int J Biochem Cell Biol. 41:2389–2397. 2009. View Article : Google Scholar : PubMed/NCBI

47 

Li J, Ran C, Li E, Gordon F, Comstock G, Siddiqui H, Cleghorn W, Chen HZ, Kornacker K, Liu CG, et al: Synergistic function of E2F7 and E2F8 is essential for cell survival and embryonic development. Dev Cell. 14:62–75. 2008. View Article : Google Scholar : PubMed/NCBI

48 

Westendorp B, Mokry M, Groot Koerkamp MJ, Holstege FC, Cuppen E and de Bruin A: E2F7 represses a network of oscillating cell cycle genes to control S-phase progression. Nucleic Acids Res. 40:3511–3523. 2012. View Article : Google Scholar : PubMed/NCBI

49 

Lundberg AS and Weinberg RA: Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol. 18:753–761. 1998. View Article : Google Scholar : PubMed/NCBI

50 

Ezhevsky SA, Ho A, Becker-Hapak M, Davis PK and Dowdy SF: Differential regulation of retinoblastoma tumor suppressor protein by G(1) cyclin-dependent kinase complexes in vivo. Mol Cell Biol. 21:4773–4784. 2001. View Article : Google Scholar : PubMed/NCBI

51 

Harbour JW, Luo RX, Dei Santi A, Postigo AA and Dean DC: Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell. 98:859–869. 1999. View Article : Google Scholar : PubMed/NCBI

52 

van den Heuvel S and Harlow E: Distinct roles for cyclin-dependent kinases in cell cycle control. Science. 262:2050–2054. 1993. View Article : Google Scholar : PubMed/NCBI

53 

Garber K: The cancer drug that almost wasn't. Science. 345:865–867. 2014. View Article : Google Scholar : PubMed/NCBI

54 

Dolman ME, Poon E, Ebus ME, den Hartog IJ, van Noesel CJ, Jamin Y, Hallsworth A, Robinson SP, Petrie K, Sparidans RW, et al: Cyclin-dependent kinase inhibitor AT7519 as a potential drug for MYCN-dependent neuroblastoma. Clin Cancer Res. 21:5100–5109. 2015. View Article : Google Scholar : PubMed/NCBI

55 

Rigas AC, Robson CN and Curtin NJ: Therapeutic potential of CDK inhibitor NU2058 in androgen-independent prostate cancer. Oncogene. 26:7611–7619. 2007. View Article : Google Scholar : PubMed/NCBI

56 

Joshi KS, Rathos MJ, Mahajan P, Wagh V, Shenoy S, Bhatia D, Chile S, Sivakumar M, Maier A, Fiebig HH and Sharma S: P276-00, a novel cyclin-dependent inhibitor induces G1-G2 arrest, shows antitumor activity on cisplatin-resistant cells and significant in vivo efficacy in tumor models. Mol Cancer Ther. 6:926–934. 2007. View Article : Google Scholar : PubMed/NCBI

57 

Joshi KS, Rathos MJ, Joshi RD, Sivakumar M, Mascarenhas M, Kamble S, Lal B and Sharma S: In vitro antitumor properties of a novel cyclin-dependent kinase inhibitor, P276-00. Mol Cancer Ther. 6:918–925. 2007. View Article : Google Scholar : PubMed/NCBI

58 

Giordano A, Rossi A, Romano G and Bagella L: Tumor suppressor pRb2/p130 gene and its derived product Spa310 spacer domain as perspective candidates for cancer therapy. J Cell Physiol. 213:403–406. 2007. View Article : Google Scholar : PubMed/NCBI

59 

De Azevedo WF, Leclerc S, Meijer L, Havlicek L, Strnad M and Kim SH: Inhibition of cyclin-dependent kinases by purine analogues: Crystal structure of human cdk2 complexed with roscovitine. Eur J Biochem. 243:518–526. 1997. View Article : Google Scholar : PubMed/NCBI

60 

Lee B, Sandhu S and McArthur G: Cell cycle control as a promising target in melanoma. Curr Opin Oncol. 27:141–150. 2015. View Article : Google Scholar : PubMed/NCBI

61 

Dange Y, Bhinge S and Salunkhe V: Optimization and validation of RP-HPLC method for simultaneous estimation of palbociclib and letrozole. Toxicol Mech Methods 1–8. 2017.

62 

Guha M: Cyclin-dependent kinase inhibitors move into Phase III. Nat Rev Drug Discov. 11:892–894. 2012. View Article : Google Scholar : PubMed/NCBI

63 

Cardoso F, Bischoff J, Brain E, Zotano ÁG, Lück HJ, Tjan-Heijnen VC, Tanner M and Aapro M: A review of the treatment of endocrine responsive metastatic breast cancer in postmenopausal women. Cancer Treat Rev. 39:457–465. 2013. View Article : Google Scholar : PubMed/NCBI

64 

Sammons SL, Topping DL and Blackwell KL: HR+, HER2 advanced breast cancer and CDK4/6 inhibitors: mode of action, clinical activity, and safety profiles. Current Cancer Drug Targets. 17:637–649. 2017. View Article : Google Scholar : PubMed/NCBI

65 

Costa R, Costa RB, Talamantes SM, Helenowski I, Peterson J, Kaplan J, Carneiro BA, Giles FJ and Gradishar WJ: Meta-analysis of selected toxicity endpoints of CDK4/6 inhibitors: Palbociclib and ribociclib. Breast. 35:1–7. 2017. View Article : Google Scholar : PubMed/NCBI

66 

Iwata H, Im SA, Masuda N, Im YH, Inoue K, Rai Y, Nakamura R, Kim JH, Hoffman JT, Zhang K, et al: PALOMA-3: Phase III trial of fulvestrant with or without palbociclib in premenopausal and postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer that progressed on prior endocrine therapy-safety and efficacy in Asian patients. J Global Oncol. 3:289–303. 2017. View Article : Google Scholar

67 

Loibl S, Turner NC, Ro J, Cristofanilli M, Iwata H, Im SA, Masuda N, Loi S, André F, Harbeck N, et al: Palbociclib combined with fulvestrant in premenopausal women with advanced breast cancer and prior progression on endocrine therapy: PALOMA-3 Results. Oncologist. 22:1028–1038. 2017. View Article : Google Scholar : PubMed/NCBI

68 

Schwartz GK, LoRusso PM, Dickson MA, Randolph SS, Shaik MN, Wilner KD, Courtney R and O'Dwyer PJ: Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br J Cancer. 104:1862–1868. 2011. View Article : Google Scholar : PubMed/NCBI

69 

Fribbens C, OLeary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, Cristofanilli M, Andre F, Loi S, Loibl S, et al: Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 34:2961–2968. 2016. View Article : Google Scholar : PubMed/NCBI

70 

Gelsomino L, Gu G, Rechoum Y, Beyer AR, Pejerrey SM, Tsimelzon A, Wang T, Huffman K, Ludlow A, Andò S and Fuqua SAW: ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling. Breast Cancer Res Treat. 157:253–265. 2016. View Article : Google Scholar : PubMed/NCBI

71 

Kuehl WM and Bergsagel PL: Molecular pathogenesis of multiple myeloma and its premalignant precursor. J Clin Invest. 122:3456–3463. 2012. View Article : Google Scholar : PubMed/NCBI

72 

Ocio EM, Mitsiades CS, Orlowski RZ and Anderson KC: Future agents and treatment directions in multiple myeloma. Expert Rev Hematol. 7:127–141. 2014. View Article : Google Scholar : PubMed/NCBI

73 

Castelli R, Gualtierotti R, Orofino N, Losurdo A, Gandolfi S and Cugno M: Current and emerging treatment options for patients with relapsed myeloma. Clin Med Insights Oncol. 7:209–219. 2013. View Article : Google Scholar : PubMed/NCBI

74 

Niesvizky R, Badros AZ, Costa LJ, Ely SA, Singhal SB, Stadtmauer EA, Haideri NA, Yacoub A, Hess G, Lentzsch S, et al: Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Leuk Lymphoma. 56:3320–3328. 2015. View Article : Google Scholar : PubMed/NCBI

75 

Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, et al: A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 348:2609–2617. 2003. View Article : Google Scholar : PubMed/NCBI

76 

Perumal D, Kuo PY, Leshchenko VV, Jiang Z, Divakar SK, Cho HJ, Chari A, Brody J, Reddy MV, Zhang W, et al: Dual targeting of CDK4 and ARK5 using a novel kinase inhibitor ON123300 exerts potent anticancer activity against multiple myeloma. Cancer Res. 76:1225–1236. 2016. View Article : Google Scholar : PubMed/NCBI

77 

Liu L, Ulbrich J, Müller J, Wüstefeld T, Aeberhard L, Kress TR, Muthalagu N, Rycak L, Rudalska R, Moll R, et al: Deregulated MYC expression induces dependence upon AMPK-related kinase 5. Nature. 483:608–612. 2012. View Article : Google Scholar : PubMed/NCBI

78 

Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, et al: Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 31:3327–3334. 2013. View Article : Google Scholar : PubMed/NCBI

79 

Liu M, Xu S, Wang Y, Li Y, Li Y, Zhang H, Liu H and Chen J: PD 0332991, a selective cyclin D kinase 4/6 inhibitor, sensitizes lung cancer cells to treatment with epidermal growth factor receptor tyrosine kinase inhibitors. Oncotarget. 7:84951–84964. 2016. View Article : Google Scholar : PubMed/NCBI

80 

Shaw AT, Winslow MM, Magendantz M, Ouyang C, Dowdle J, Subramanian A, Lewis TA, Maglathin RL, Tolliday N and Jacks T: Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress. Proc Natl Acad Sci USA. 108:pp. 8773–8778. 2011; View Article : Google Scholar : PubMed/NCBI

81 

Montagut C and Settleman J: Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Lett. 283:125–134. 2009. View Article : Google Scholar : PubMed/NCBI

82 

Tao Z, Le Blanc JM, Wang C, Zhan T, Zhuang H, Wang P, Yuan Z and Lu B: Coadministration of trametinib and palbociclib radiosensitizes KRAS-mutant non-small cell lung cancers in vitro and in vivo. Clin Cancer Res. 22:122–133. 2016. View Article : Google Scholar : PubMed/NCBI

83 

Cancer Genome Atlas Research Network, . Comprehensive genomic characterization of squamous cell lung cancers. Nature. 489:519–525. 2012. View Article : Google Scholar : PubMed/NCBI

84 

Chikara S, Lindsey K, Dhillon H, Mamidi S, Kittilson J, Christofidou-Solomidou M and Reindl KM: Enterolactone induces G1-phase cell cycle arrest in nonsmall cell lung cancer cells by downregulating cyclins and cyclin-dependent kinases. Nutr Cancer. 69:652–662. 2017. View Article : Google Scholar : PubMed/NCBI

85 

Chen DH and Zhang XS: Targeted therapy: Resistance and re-sensitization. Chin J Cancer. 34:496–501. 2015. View Article : Google Scholar : PubMed/NCBI

86 

Lee JE, Park HS, Lee D, Yoo G, Kim T, Jeon H, Yeo MK, Lee CS, Moon JY, Jung SS, et al: Hippo pathway effector YAP inhibition restores the sensitivity of EGFR-TKI in lung adenocarcinoma having primary or acquired EGFR-TKI resistance. Biochem Biophys Res Commun. 474:154–160. 2016. View Article : Google Scholar : PubMed/NCBI

87 

Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay MR, Ward RA, Mellor MJ, et al: AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 4:1046–1061. 2014. View Article : Google Scholar : PubMed/NCBI

88 

Luque-Cabal M, García-Teijido P, Fernández-Pérez Y, Sánchez-Lorenzo L and Palacio-Vázquez I: Mechanisms behind the resistance to trastuzumab in her2-amplified breast cancer and strategies to overcome it. Clin Med Insights Oncol. 10 Suppl 1:S21–S30. 2016.

89 

Teh JL, Purwin TJ, Greenawalt EJ, Chervoneva I, Goldberg A, Davies MA and Aplin AE: An in vivo reporter to quantitatively and temporally analyze the effects of CDK4/6 inhibitor-based therapies in melanoma. Cancer Res. 76:5455–5466. 2016. View Article : Google Scholar : PubMed/NCBI

90 

Kwiatkowski N, Zhang T, Rahl PB, Abraham BJ, Reddy J, Ficarro SB, Dastur A, Amzallag A, Ramaswamy S, Tesar B, et al: Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 511:616–620. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu M, Liu H and Chen J: Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review). Oncol Rep 39: 901-911, 2018.
APA
Liu, M., Liu, H., & Chen, J. (2018). Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review). Oncology Reports, 39, 901-911. https://doi.org/10.3892/or.2018.6221
MLA
Liu, M., Liu, H., Chen, J."Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review)". Oncology Reports 39.3 (2018): 901-911.
Chicago
Liu, M., Liu, H., Chen, J."Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review)". Oncology Reports 39, no. 3 (2018): 901-911. https://doi.org/10.3892/or.2018.6221
Copy and paste a formatted citation
x
Spandidos Publications style
Liu M, Liu H and Chen J: Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review). Oncol Rep 39: 901-911, 2018.
APA
Liu, M., Liu, H., & Chen, J. (2018). Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review). Oncology Reports, 39, 901-911. https://doi.org/10.3892/or.2018.6221
MLA
Liu, M., Liu, H., Chen, J."Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review)". Oncology Reports 39.3 (2018): 901-911.
Chicago
Liu, M., Liu, H., Chen, J."Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review)". Oncology Reports 39, no. 3 (2018): 901-911. https://doi.org/10.3892/or.2018.6221
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team