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 language | English |
|---|---|
| Pages (from-to) | 549-565 |
| Number of pages | 17 |
| Journal | Expert Opinion on Pharmacotherapy |
| Volume | 12 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Mar 2011 |
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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 journal › Article
}
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 -