Mechanism of Action

Role of PARP enzymes in DNA repair
PARP enzymes and BRCA1/2 proteins both function in DNA repair2,3
NORMAL CELLS
Normal cells image 1
Normal cells image 2
In normal cells
  • The role of PARP enzymes is to repair single-strand breaks (SSBs) in DNA generated during DNA replication or by DNA damage2
  • The role of BRCA1/2 proteins is to repair double-strand breaks (DSBs) in DNA via a repair mechanism called homologous recombination (HR)3
CANCER CELLS
Cancer cells image 1
Cancer cells image 2
In cancer cells
  • In gBRCA-mutated cells, HR, the mechanism that repairs harmful DSBs in DNA, is defective3,4
  • These cells become reliant on PARP enzymes, in addition to other, less accurate repair mechanisms, to maintain DNA repair and cell proliferation3,4
  • Cancer cell overreliance on these alternative repair mechanisms can lead to the accumulation of genetic mutations, promoting the formation and survival of tumor cells4
Dual mechanism of action
TALZENNA is a targeted treatment that induces cancer cell death via 2 complementary mechanisms1*
PARP ENZYME INHIBITION
PARP enzyme inhibition image
HIGHLY POTENT PARP TRAPPING
PARP trapping image
  • PARP enzymatic inhibition disrupts the subsequent recruitment of DNA repair proteins to the site of SSBs. This results in the accumulation of SSBs, which eventually leads to DSBs during DNA replication5,6
  • In vitro studies demonstrated that BRCA1/2-mutated, HR-deficient cells are highly sensitive to cell death induced by TALZENNA6,7
  • Preclinical studies have shown that TALZENNA has the capacity to trap PARP enzymes to DNA, forming PARP-DNA complexes6,7
  • In preclinical studies, TALZENNA demonstrated highly potent PARP trapping, which may be correlated with tumor cell death6,7
*TALZENNA can also affect healthy cells.
REFERENCES
  1. TALZENNA [prescribing information]. New York, NY: Pfizer Inc.; 2020.
  2. Sonnenblick A, de Azambuja E, Azim HA Jr, Piccart M. An update on PARP inhibitors—moving to the adjuvant setting. Nat Rev Clin Oncol. 2015;12(1):27-41.
  3. Lee J-m, Ledermann JA, Kohn EC. PARP inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol. 2014;25(1):32-40.
  4. Lupo B, Trusolino L. Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited. Biochim Biophys Acta. 2014;1846(1):201-215.
  5. Livraghi L, Garber JE. PARP inhibitors in the management of breast cancer: current data and future prospects. BMC Med. 2015;13:188. doi:10.1186/s12916-015-0425-1.
  6. Gavande NS, VanderVere-Carozza PS, Hinshaw HD, et al. DNA repair targeted therapy: the past or future of cancer treatment? Pharmacol Ther. 2016;160:65-83.
  7. Murai J, Huang SY, Renaud A, et al. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther. 2014;13(2):433-443.
  8. Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379(8):753-763.