HER2 Support Group Forums - View Single Post - Gene Profiling Predicts Resistance To Breast Cancer Drug Herceptin

Lani · 02-20-2007, 01:01 PM

and reverse herceptin resistance. It was done on SKBr3 (her2+er-) but in its discussion opined that triple positive bc would probably need treatment with an her2inhibitor, IGFR inhibitor and ER inhibitor(?lapatinib+AIor faslodex?):

http://mct.aacrjournals.org/cgi/content/full/6/2/667

Lapatinib induces apoptosis in
trastuzumab-resistant breast cancer
cells: effects on insulin-like growth
factor I signaling

Rita Nahta, F. Esteva, et al

Abstract
The majority of breast cancer patients who achieve an initial therapeutic response to the HER2-targeted
antibody trastuzumab will show disease progression within 1 year. Thus, the identification of novel agents
that effectively inhibit survival of cancer cells that have progressed on trastuzumab is critical. In the current
study, we show that the dual epidermal growth factor receptor (EGFR)/human EGFR-2 (HER2) kinase
inhibitor lapatinib induces apoptosis in trastuzumab-resistant cells derived from the HER2-overexpressing
SKBR3 breast cancer line. Lapatinib inhibited EGFR and HER2 signaling in resistant cells, blocking
activation of downstream Akt, mitogen-activated protein kinase, and S6 kinases and inducing expression of
p27kip1. Importantly, lapatinib also inhibited insulin-like growth factor I (IGF-I) signaling and growth-
promoting effects in parental and resistant cells, and the cytotoxic effects of lapatinib were further enhanced
by the IGF-I receptor–blocking antibody IR3. As increased IGF-I receptor signaling has been implicated in
trastuzumab resistance, our data strongly support further study of lapatinib as a potential therapeutic in
breast cancers that have progressed on trastuzumab. [Mol Cancer Ther 2007;6(2):667–74]

02-20-2007, 01:01 PM	#3
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	just read this today--lapatinib tends to work on EGFR, IGFR simultaneously and reverse herceptin resistance. It was done on SKBr3 (her2+er-) but in its discussion opined that triple positive bc would probably need treatment with an her2inhibitor, IGFR inhibitor and ER inhibitor(?lapatinib+AIor faslodex?): http://mct.aacrjournals.org/cgi/content/full/6/2/667 Lapatinib induces apoptosis in trastuzumab-resistant breast cancer cells: effects on insulin-like growth factor I signaling Rita Nahta, F. Esteva, et al Abstract The majority of breast cancer patients who achieve an initial therapeutic response to the HER2-targeted antibody trastuzumab will show disease progression within 1 year. Thus, the identification of novel agents that effectively inhibit survival of cancer cells that have progressed on trastuzumab is critical. In the current study, we show that the dual epidermal growth factor receptor (EGFR)/human EGFR-2 (HER2) kinase inhibitor lapatinib induces apoptosis in trastuzumab-resistant cells derived from the HER2-overexpressing SKBR3 breast cancer line. Lapatinib inhibited EGFR and HER2 signaling in resistant cells, blocking activation of downstream Akt, mitogen-activated protein kinase, and S6 kinases and inducing expression of p27kip1. Importantly, lapatinib also inhibited insulin-like growth factor I (IGF-I) signaling and growth- promoting effects in parental and resistant cells, and the cytotoxic effects of lapatinib were further enhanced by the IGF-I receptor–blocking antibody IR3. As increased IGF-I receptor signaling has been implicated in trastuzumab resistance, our data strongly support further study of lapatinib as a potential therapeutic in breast cancers that have progressed on trastuzumab. [Mol Cancer Ther 2007;6(2):667–74]