Mechanism of action

In hormone receptor positive (HR+) breast cancer, the presence of estrogen causes overactive signaling of proteins within the nucleus.2,3

Increased activity of cyclin-dependent kinase 4/6 (CDK4/6) that initiates the transition from G1 to the S phase can lead to a loss of proliferative control.2,4

The inhibition of CDK4/6 by IBRANCE® helps restore control by inducing G1 arrest and reducing cell cycle progression.5

IBRANCE® improves the anti-proliferative effects of endocrine therapy (ET) through synergistic inhibition of both upstream and downstream components of the estrogen receptor (ER) pathway.5-7

The combination of IBRANCE® with ET results in increased and sustained cell-cycle arrest compared to ET alone.5-7

In a number of cancers , the dysregulation of the cyclin D1-CDK 4/6-Rb pathway has been associated with a loss of proliferative control.4,8-10 Pre-clinical studies demonstrate that inhibiting CDKs 4 and 6 in tumour cells blocks retinoblastoma tumor suppressor protein (RB) phosphorylation, and therefore cell proliferation.11

endocrine_therapies

 

References

  1. IBRANCE® Summary of Product Characteristics.
  2. Prall OW, et al. J Biol Chem. 1997;272:10882-10894. 
  3. Altucci L, et al. Oncogene. 1996;12(11):2315‐2324. 
  4. Weinberg RA. pRb and control of the cell cycle clock. The Biology of Cancer. 2nd ed.  New York, NY: Garland Science; 2014.
  5. Rocca A, et al. Expert Opin Pharmacother. 2014;15(3):407-420. 
  6. Cadoo KA, et al. Breast Cancer (Dove Med Press). 2014;6:123-133. 
  7. Khoehler M, et al. Ann Oncol. 2014;25 (Suppl 1): i21-i22.
  8. Wolfel T, et al. Science. 1995; 269(5228):1281-1284.
  9. Kanoe H, et al. Anticancer Res. 1998;18(4A):2317-2321.
  10. An H-X, et al. Am J Pathol. 1999;154(1):113-118.
  11. Fry DW, et al. Mol Cancer Ther. 2004;3:1427-1437.

 

PP-IBR-IRL-0288
Date of preparation: March 2020

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.