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HER2-positive breast cancer: cotargeting to overcome treatment resistance

Paola Zagami1,2,3, Luca Boscolo Bielo1,2, Eleonora Nicolò1,2,4

  • 1Division of Early Drug Development for Innovative Therapies, European Institute of Oncology IRCCS.

Current Opinion in Oncology
|August 25, 2023
PubMed
Abstract

Insights

Cotargeting HER2 (human epidermal growth factor receptor 2) with other pathways can overcome resistance in HER2-positive breast cancer. This strategy shows promise for improving patient outcomes in this heterogeneous disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Anti-HER2 (human epidermal growth factor receptor 2) agents have significantly improved outcomes for HER2-positive breast cancer.
  • However, primary and secondary resistance limit treatment efficacy in a subset of patients.
  • Understanding HER2+ breast cancer heterogeneity is crucial for developing new therapeutic strategies.

Purpose of the Study:

  • To review current data on cotargeting HER2 with other signaling pathways to overcome resistance to anti-HER2 therapies.
  • To explore novel therapeutic combinations for HER2-positive breast cancer.

Main Methods:

  • Literature review of studies investigating cotargeting strategies in HER2-positive breast cancer.
  • Analysis of data on novel predictive biomarkers and therapeutic targets.
  • Synthesis of findings on combinations involving HER2 with hormone receptors, PI3K pathway, other HERs receptors, and immune checkpoints.

Main Results:

  • Novel predictive biomarkers are emerging to guide response to anti-HER2 treatments.
  • Cotargeting HER2 with hormone receptors is a validated approach for HER2+/HR+ breast cancer.
  • Combinations targeting HER2 with PI3K pathway, other HERs receptors, or immune checkpoints show promising results.

Conclusions:

  • HER2-positive breast cancer is a heterogeneous disease requiring tailored treatment approaches.
  • Cotargeting HER2 with complementary signaling pathways can enhance treatment efficacy and overcome resistance.
  • Continued research into novel targets and combinations is essential for advancing treatment regimens.

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