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 journalArticle

7 Citations (Scopus)

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

Fingerprint

Breast Neoplasms
Therapeutics
Expert Testimony
Biological Factors
Receptor Protein-Tyrosine Kinases
Metabolic Networks and Pathways
Combination Drug Therapy
Drug Resistance
Monoclonal Antibodies
Clinical Trials
Pharmacology
Phenotype
Drug Therapy
Pharmaceutical Preparations
Neoplasms
Trastuzumab

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

Cite this

Hitting multiple targets in HER2-positive breast cancer : Proof of principle or therapeutic opportunity? / Geuna, Elena; Milani, Andrea; Redana, Stefania; Rossi, Valentina; Valabrega, Giorgio; Aglietta, Massimo; Montemurro, Filippo.

In: Expert Opinion on Pharmacotherapy, Vol. 12, No. 4, 03.2011, p. 549-565.

Research output: Contribution to journalArticle

@article{67a12b1dc2544806802a7ad0e7895b96,
title = "Hitting multiple targets in HER2-positive breast cancer: Proof of principle or therapeutic opportunity?",
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.",
keywords = "Breast cancer, Endocrine therapy, HDAC inhibitors, HER2, HSP90 inhibitors, IGF-1R, Lapatinib, mTOR inhibitors, Neratinib, Pazopanib, Pertuzumab, Trastuzumab",
author = "Elena Geuna and Andrea Milani and Stefania Redana and Valentina Rossi and Giorgio Valabrega and Massimo Aglietta and Filippo Montemurro",
year = "2011",
month = "3",
doi = "10.1517/14656566.2011.525218",
language = "English",
volume = "12",
pages = "549--565",
journal = "Expert Opinion on Pharmacotherapy",
issn = "1465-6566",
publisher = "Taylor and Francis Ltd.",
number = "4",

}

TY - JOUR

T1 - Hitting multiple targets in HER2-positive breast cancer

T2 - Proof of principle or therapeutic opportunity?

AU - Geuna, Elena

AU - Milani, Andrea

AU - Redana, Stefania

AU - Rossi, Valentina

AU - Valabrega, Giorgio

AU - Aglietta, Massimo

AU - Montemurro, Filippo

PY - 2011/3

Y1 - 2011/3

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Endocrine therapy

KW - HDAC inhibitors

KW - HER2

KW - HSP90 inhibitors

KW - IGF-1R

KW - Lapatinib

KW - mTOR inhibitors

KW - Neratinib

KW - Pazopanib

KW - Pertuzumab

KW - Trastuzumab

UR - http://www.scopus.com/inward/record.url?scp=79951610766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951610766&partnerID=8YFLogxK

U2 - 10.1517/14656566.2011.525218

DO - 10.1517/14656566.2011.525218

M3 - Article

C2 - 21208143

AN - SCOPUS:79951610766

VL - 12

SP - 549

EP - 565

JO - Expert Opinion on Pharmacotherapy

JF - Expert Opinion on Pharmacotherapy

SN - 1465-6566

IS - 4

ER -