Related Experiment Video

Updated: Feb 12, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
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Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

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Trastuzumab-Resistant HER2+ Breast Cancer Cells Retain Sensitivity to Poly (ADP-Ribose) Polymerase (PARP) Inhibition

Monica E Wielgos1, Zhuo Zhang1, Rajani Rajbhandari1

  • 1Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.

Molecular Cancer Therapeutics
|March 30, 2018
PubMed

Insights

Poly (ADP-ribose) polymerase inhibitors (PARPi) show promise against HER2-positive breast cancer resistant to trastuzumab. PARPi reduced tumor growth by inhibiting PARP-1 and affecting NF-κB signaling, suggesting a new therapeutic avenue.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • HER2-targeted therapies like trastuzumab improve survival for HER2-positive breast cancer.
  • Tumor resistance to trastuzumab remains a significant clinical challenge.
  • Previous studies indicated an unexpected sensitivity of HER2-positive cells to PARP inhibitors (PARPi).

Purpose of the Study:

  • To investigate the efficacy of PARPi in HER2-positive trastuzumab-resistant (TR) breast cancer cells.
  • To elucidate the underlying mechanisms of PARPi-induced cytotoxicity in this context.

Main Methods:

  • Utilized the PARPi ABT-888 (veliparib) in vitro and in vivo models of HER2-positive TR breast cancer.
  • Employed PARP-1 siRNA to confirm the role of PARP-1 inhibition.
  • Assessed NF-κB pathway activity, including p65 binding and IL8 gene/protein expression.

Main Results:

  • Veliparib demonstrated significant reduction in cell survival and tumor growth of HER2-positive TR cells.
  • PARP-1 inhibition was confirmed as a key contributor to PARPi's cytotoxic effects.
  • PARP-1 silencing modulated NF-κB activity, decreasing IL8 expression.

Conclusions:

  • PARPi exhibit anti-tumor activity in HER2-positive trastuzumab-resistant breast cancer.
  • PARPi-induced cytotoxicity involves PARP-1 inhibition and subsequent effects on NF-κB signaling.
  • These findings support the clinical investigation of PARPi for patients with refractory HER2-positive breast cancer.

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