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Published on: January 22, 2019

Inhibitors of IAP/XIAP enhance activity of sacituzumab govitecan

Ming Zhao1, Bailiang Wang1, Kurt W Evans1

  • 1Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Journal of the National Cancer Institute
|August 8, 2026
PubMed

Insights

Combining sacituzumab govitecan (SG) with inhibitor of apoptosis protein (IAP) antagonists shows promise for advanced breast cancer. This preclinical study found that IAP inhibitors enhance SG

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Sacituzumab govitecan (SG) is an approved TROP2 antibody-drug conjugate for advanced breast cancer.
  • Intrinsic and acquired resistance limit the efficacy of SG, necessitating novel therapeutic strategies.
  • Inhibitor of apoptosis proteins (IAPs) are key regulators of cell death pathways.

Purpose of the Study:

  • To investigate the potential of combining SG with IAP antagonists to overcome resistance and enhance anti-cancer activity.
  • To evaluate the synergistic effects of SG and IAP inhibitors in preclinical breast cancer models.

Main Methods:

  • Utilized breast cancer cell lines and patient-derived xenografts (PDXs) for preclinical evaluation.
  • Conducted combination therapy studies with SG and IAP inhibitors (birinapant, tolinapant).
  • Assessed antitumor activity, event-free survival, cell viability, colony formation, and apoptosis induction in vitro and in vivo.

Main Results:

  • IAP antagonists, particularly birinapant, enhanced the antitumor activity of SG in preclinical models.
  • Combination therapy with SG and IAP inhibitors demonstrated greater antitumor efficacy and prolonged event-free survival compared to SG alone.
  • In vitro studies showed significant synergy between IAP antagonists and SG in inhibiting cell viability, colony formation, and inducing apoptosis.

Conclusions:

  • Combination of sacituzumab govitecan with IAP inhibitors represents a promising therapeutic strategy for advanced breast cancer.
  • IAP antagonists may overcome resistance mechanisms and potentiate the activity of SG.
  • Further clinical investigation is warranted to validate these findings in breast cancer patients.

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