CDK inhibitor

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CDK inhibitors are a relatively new group of drugs that are used to treat various cancers (e.g. breast cancer ). CDK inhibitors are inhibitors of protein kinases cyclin-dependent kinases (engl. C yclin- d ependent k inases, CDKs) which, when the control of the cell cycle and thus in the cell proliferation play a role.

Protein kinases are enzymes that phosphorylate other proteins at specific locations . There are 20 different CDKs in humans.

First representative

The first representative of the CDK inhibitors, palbociclib (trade name: Ibrance , manufacturer: Pfizer ), was approved by the US regulatory agency (FDA) in March 2015 . Palbociclib inhibits CDK4 and CDK6 and has also been approved in the EU since November 2016 for the treatment of hormone receptor-positive / HER2-negative locally advanced or metastatic breast cancer.

At the end of August 2017, the EU Commission approved ribociclib (trade name: Kisqali , manufacturer: Novartis ) - in combination with an aromatase inhibitor - for the treatment of postmenopausal women with a hormone receptor (HR) -positive, human epidermal growth factor receptor-2 (HER2) - negative, locally advanced or metastatic breast cancer (breast cancer) approved as an initial endocrine-based therapy. The therapy can be administered orally. Kisqali was previously approved in the United States in March 2017.

Another CDK inhibitor is abemaciclib (trade name: Verzenio , manufacturer: Lilly , approved in the USA since September 28, 2017, in the EU since September 27, 2018).

Candidates

Next are Briciclib (manufacturer: Onconova ) Dinaciclib (Manufacturer: MSD ) Milciclib , Riviciclib , Roniciclib , Seliciclib and Voruciclib in development.

literature

  • Barroso-Sousa R et al. (2016): Clinical Development of the CDK4 / 6 Inhibitors Ribociclib and Abemaciclib in Breast Cancer. Breast Care (Basel). 11 (3): 167-73. doi: 10.1159 / 000447284
  • Hortobagyi GN et al. (2016): Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer, N Engl J Med 2016; 375: 1738-48. doi: 10.1056 / NEJMoa1609709 PMID 27717303
  • Knudsen ES et al. (2015): The history and future of targeting cyclin-dependent kinases in cancer therapy, Nat Rev Drug Discov. 2015 Feb; 14 (2): 130-146. doi: 10.1038 / nrd4504
  • O'Leary B et al. (2016): Treating cancer with selective CDK4 / 6 inhibitors. Nat Rev Clin Oncol. 13: 417-430. doi: 10.1038 / nrclinonc.2016.26
  • Patnaik A et al. (2016): Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid Tumors. Cancer Discov. 6 (7): 740-53. doi: 10.1158 / 2159-8290.CD-16-0095

See also

Web links

http://www.kisqali.com/

Individual evidence

  1. ↑ Marcos Malumbres, Mariano Barbacid : Cell cycle, CDKs and cancer: a changing paradigm. In: Nature Reviews Cancer. 9, 2009, p. 153, doi: 10.1038 / nrc2602 .
  2. ↑ Phylogenetic analysis of CDK and cyclin proteins in premetazoan lineages . Cao et al. (2014), doi: 10.1186 / 1471-2148-14-10 .
  3. ↑ Drugs @ FDA: FDA Approved Drug Products - Ibrance (Palbociclib) .
  4. ^ Community register of medicinal products for human use .
  5. ↑ Ibrance: Summary of Product Characteristics .
  6. ↑ approved first Cdk4 / 6 inhibitors in Europe , Cancer Information Service, accessed on September 20 2017th
  7. ↑ SUMMARY OF DRUG EMA CHARACTERISTICS , accessed September 20, 2017.
  8. ↑ HIGHLIGHTS OF PRESCRIBING INFORMATION FDA, accessed September 20, 2017.
  9. ↑ FDA approves new treatment for certain advanced or metastatic breast cancers , PM FDA dated September 28, 2017, accessed December 4, 2017
  10. ↑ Abemaciclib: Third Cdk4 / 6 inhibitor approved in Europe. In: Cancer Information Service. German Cancer Research Center, October 8, 2018, accessed on March 17, 2019 .
  11. ↑ pipeline site Onconova, accessed on September 20 2017th
  12. ↑ Efficacy and safety of dinaciclib versus ofatumumab in patients with relapsed / refractory chronic lymphocytic leukemia Blood January 26, 2017, accessed September 20, 2017.