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Talzenna MoA

For TALZENNA® (talazoparib) Prescribing Information click here.

The content of this website has been produced in line with the Talzenna Summary of Product Characteristics for the United Kingdom. Talzenna (talazoparib) Prescribing Information for The United Kingdom click here. Adverse event reporting information can be found at the bottom of the page.

Mechanism of Action


TALZENNA® + enzalutamide: Complementary Mechanisms of Action that enhance one another.1



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Mechanism of Action Video: TALZENNA® + enzalutamide

The video highlights the combination of talazoparib, a PARP inhibitor, with enzalutamide, an androgen receptor inhibitor, which enhances treatment efficacy by preventing cancer cells from repairing their DNA, leading to cell death.



How do PARPi and ARPi work together?

TALZENNA®
  • a strong inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes with highly potent PARP trapping.1
  • Cells deficient in homologous recombination repair (HRR) genes are unable to repair double-stranded breaks (DSBs) in DNA and become reliant on PARP-triggered DNA repair mechanism for maintaining genome integrity.1
  • HRR-deficient cells are highly sensitive to cell death induced by the PARP enzyme inhibitor TALZENNA®.1
  • TALZENNA® demonstrated highly potent PARP trapping, which is considered to be correlated with tumour cell death.1
Enzalutamide
  • a direct androgen receptor inhibitor (ARi) acts on multiple steps of the AR signaling pathway, which may lead to decreased proliferation, tumour cell death, and reduced tumour volume.2

The interaction of PARP inhibitors and AR inhibitors, has the ability to elicit anti-tumour effects, independent of initial HRR gene status.1, 2 

PARP (poly ADP-ribose polymerase) inhibitors have traditionally been used in HRR-deficient cells to impair the cellular detection of DNA damage. Preclinical data have demonstrated interdependencies between the androgen receptor (AR) and PARP that could be therapeutically exploited by combining PARP inhibitors and AR pathway inhibitors, irrespective of HRR deficiencies. Coadministration of these treatments may lead to substantial clinical benefit, possibly delay resistance, and provide an additional therapeutic treatment for men with mCRPC.

Please refer to the enzalutamide Summary of Product Characteristics (SmPC) for recommended dosing information about enzalutamide.

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Abbreviations:

MOA - Mechanism of Action, mCRPC - Metastatic Castration-Resistant Prostate Cancer, PARPi - Poly ADP-ribose Polymerase, ARPi - Androgen Receptor Inhibitor, AR - Androgen Receptor, DNA - Deoxyribonucleic Acid, HRR - Homologous Recombination Repair, DSBs - Double-Stranded Breaks, SSB - Singe-Stranded Break

References

1. TALZENNA® (talazoparib) Summary of Product Characteristics for United Kingdom. Available on www.medicines.org.uk   
2. Agarwal N, Azad AA, Carles J, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet 2023;1-13. [Accessed: May 2025]. 

PP-TXT-GBR-0035  May 2025

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