Hitting multiple targets in HER2-positive breast cancer: Proof of principle or therapeutic opportunity?

Elena Geuna, Andrea Milani, Stefania Redana, Valentina Rossi, Giorgio Valabrega, Massimo Aglietta, Filippo Montemurro

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Pharmacological targeting of the tyrosine kinase receptor HER2 with the monoclonal antibody trastuzumab has dramatically changed the outlook of HER2-positive breast cancer patients. However, HER2 is part of a more complex biological network that, when deregulated, plays a central role in sustaining the cancer phenotype. These interactions account for primary or acquired resistance to drugs that hit a single biological target, like trastuzumab. Several preclinical models suggest that simultaneous targeting of crucial metabolic pathways has the potential to circumvent or delay the onset of resistance phenomena in HER2-positive breast cancer cells. Areas covered: This review describes the rationale and results of clinical trials using biologically targeted agents in HER2-positive breast cancer patients. Single drugs that hit multiple targets and cocktails of biologically targeted agents are considered, whereas combinations with chemotherapy are not addressed. Expert opinion: Most of the studies using biological agents to hit multiple targets in HER2-positive breast cancer patients confirm that resistance to single-agent HER2-targeting can be overcome. Further developments will include combination of multi-targeting strategies with chemotherapy in patients with earlier-stage disease. In addition, it is possible that newer molecular predictive factors may allow a more rationale choice of the most appropriate targeting for each individual patient.

Original languageEnglish
Pages (from-to)549-565
Number of pages17
JournalExpert Opinion on Pharmacotherapy
Volume12
Issue number4
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Breast cancer
  • Endocrine therapy
  • HDAC inhibitors
  • HER2
  • HSP90 inhibitors
  • IGF-1R
  • Lapatinib
  • mTOR inhibitors
  • Neratinib
  • Pazopanib
  • Pertuzumab
  • Trastuzumab

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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