Abstract
HER2-positive breast cancer (HER2 + BC)represents 15–20% of all BCs. In the last two decades, the introduction of monoclonal antibodies (MoAbs), tyrosine kinase inhibitors (TKIs)and antibody-drug conjugates (ADCs)directed against HER2 impressively improved patient prognosis in all disease stages. Yet, not all patients with limited-stage disease are cured, and HER2+ metastatic BC (mBC)remains an almost invariably deadly disease. Primary or acquired resistance to anti-HER2 therapies is responsible for most treatment failures. In recent years, several resistance mechanisms have been identified, such as impaired drug binding to HER2, constitutive activation of signaling pathways parallel or downstream of HER2, metabolic reprogramming or reduced immune system activation. However, only a few of them have been validated in clinical series; moreover, in the era of standard-of-care dual HER2 blockade, these mechanisms should be re-assessed and, in case, confirmed with anti-HER2 combinations. Defining the best strategies to delay or revert resistance to anti-HER2 treatments will be crucial to improve their clinical efficacy.
| Original language | English |
|---|---|
| Pages (from-to) | 53-66 |
| Number of pages | 14 |
| Journal | Critical Reviews in Oncology/Hematology |
| Volume | 139 |
| DOIs | |
| Publication status | Published - Jul 2019 |
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Keywords
- HER2-positive breast cancer
- Lapatinib
- Resistance mechanisms
- T-DM1
- T-DM1Pertuzumab
- Trastuzumab
ASJC Scopus subject areas
- Hematology
- Oncology
Cite this
Resistance mechanisms to anti-HER2 therapies in HER2-positive breast cancer : Current knowledge, new research directions and therapeutic perspectives. / Vernieri, Claudio; Milano, Monica; Brambilla, Marta; Mennitto, Alessia; Maggi, Claudia; Cona, Maria Silvia; Prisciandaro, Michele; Fabbroni, Chiara; Celio, Luigi; Mariani, Gabriella; Bianchi, Giulia Valeria; Capri, Giuseppe; de Braud, Filippo.
In: Critical Reviews in Oncology/Hematology, Vol. 139, 07.2019, p. 53-66.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Resistance mechanisms to anti-HER2 therapies in HER2-positive breast cancer
T2 - Current knowledge, new research directions and therapeutic perspectives
AU - Vernieri, Claudio
AU - Milano, Monica
AU - Brambilla, Marta
AU - Mennitto, Alessia
AU - Maggi, Claudia
AU - Cona, Maria Silvia
AU - Prisciandaro, Michele
AU - Fabbroni, Chiara
AU - Celio, Luigi
AU - Mariani, Gabriella
AU - Bianchi, Giulia Valeria
AU - Capri, Giuseppe
AU - de Braud, Filippo
PY - 2019/7
Y1 - 2019/7
N2 - HER2-positive breast cancer (HER2 + BC)represents 15–20% of all BCs. In the last two decades, the introduction of monoclonal antibodies (MoAbs), tyrosine kinase inhibitors (TKIs)and antibody-drug conjugates (ADCs)directed against HER2 impressively improved patient prognosis in all disease stages. Yet, not all patients with limited-stage disease are cured, and HER2+ metastatic BC (mBC)remains an almost invariably deadly disease. Primary or acquired resistance to anti-HER2 therapies is responsible for most treatment failures. In recent years, several resistance mechanisms have been identified, such as impaired drug binding to HER2, constitutive activation of signaling pathways parallel or downstream of HER2, metabolic reprogramming or reduced immune system activation. However, only a few of them have been validated in clinical series; moreover, in the era of standard-of-care dual HER2 blockade, these mechanisms should be re-assessed and, in case, confirmed with anti-HER2 combinations. Defining the best strategies to delay or revert resistance to anti-HER2 treatments will be crucial to improve their clinical efficacy.
AB - HER2-positive breast cancer (HER2 + BC)represents 15–20% of all BCs. In the last two decades, the introduction of monoclonal antibodies (MoAbs), tyrosine kinase inhibitors (TKIs)and antibody-drug conjugates (ADCs)directed against HER2 impressively improved patient prognosis in all disease stages. Yet, not all patients with limited-stage disease are cured, and HER2+ metastatic BC (mBC)remains an almost invariably deadly disease. Primary or acquired resistance to anti-HER2 therapies is responsible for most treatment failures. In recent years, several resistance mechanisms have been identified, such as impaired drug binding to HER2, constitutive activation of signaling pathways parallel or downstream of HER2, metabolic reprogramming or reduced immune system activation. However, only a few of them have been validated in clinical series; moreover, in the era of standard-of-care dual HER2 blockade, these mechanisms should be re-assessed and, in case, confirmed with anti-HER2 combinations. Defining the best strategies to delay or revert resistance to anti-HER2 treatments will be crucial to improve their clinical efficacy.
KW - HER2-positive breast cancer
KW - Lapatinib
KW - Resistance mechanisms
KW - T-DM1
KW - T-DM1Pertuzumab
KW - Trastuzumab
UR - http://www.scopus.com/inward/record.url?scp=85065156846&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065156846&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2019.05.001
DO - 10.1016/j.critrevonc.2019.05.001
M3 - Review article
C2 - 31112882
AN - SCOPUS:85065156846
VL - 139
SP - 53
EP - 66
JO - Critical Reviews in Oncology/Hematology
JF - Critical Reviews in Oncology/Hematology
SN - 1040-8428
ER -