PMID- 25669172
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20191210
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Print)
IS  - 1010-4283 (Linking)
VI  - 36
IP  - 7
DP  - 2015 Jul
TI  - Dacomitinib (PF-00299804), a second-generation irreversible pan-erbB receptor 
      tyrosine kinase inhibitor, demonstrates remarkable activity against 
      HER2-amplified uterine serous endometrial cancer in vitro.
PG  - 5505-13
LID - 10.1007/s13277-015-3218-4 [doi]
AB  - Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer 
      that carries an extremely poor prognosis. Up to 35 % of USC may overexpress the 
      epidermal growth factor receptor-2 (HER2/neu) at strong (i.e., 3+) level by 
      immunohistochemistry (IHC) or harbor HER2/neu gene amplification by fluorescence 
      in situ hybridization (FISH). In this study, we assessed the sensitivity of a 
      panel of USC cell lines with and without HER2/neu gene amplification to 
      dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor 
      receptor tyrosine kinase inhibitor. Eight primary cell lines (i.e., four 
      harboring HER2/neu gene amplification by FISH and four FISH- cell lines), all 
      demonstrating similar in vitro growth rates, were evaluated in 
      viability/proliferation assays. The effect of dacomitinib on cell growth, cell 
      cycle distribution, and signaling was determined using flow cytometry-based 
      assays. Dacomitinib caused a significantly stronger growth inhibition in HER2/neu 
      FISH+ USC cell lines when compared to FISH- USC (dacomitinib half maximal 
      inhibitory concentration (IC50) mean +/- SEM = 0.02803 +/- 0.003355 muM in FISH+ 
      versus 1.498 +/- 0.2209 muM in FISH- tumors, P < 0.0001). Dacomitinib growth 
      inhibition was associated with a significant and dose-dependent decline in 
      phosphorylated HER2/neu and S6 transcription factor and a dose-dependent and 
      time-dependent cell cycle arrest in G0/G1 in FISH+ USC. Dacomitinib is remarkably 
      effective against chemotherapy-resistant HER2/neu gene-amplified USC. Clinical 
      studies with dacomitinib in HER2/neu FISH+ USC patients resistant to standard 
      salvage chemotherapy are warranted.
FAU - Zhu, Liancheng
AU  - Zhu L
AD  - Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University 
      School of Medicine, Rm. 305 LSOG, 333 Cedar Street, PO Box 208063, New Haven, CT, 
      06520-8063, USA.
FAU - Lopez, Salvatore
AU  - Lopez S
FAU - Bellone, Stefania
AU  - Bellone S
FAU - Black, Jonathan
AU  - Black J
FAU - Cocco, Emiliano
AU  - Cocco E
FAU - Zigras, Tiffany
AU  - Zigras T
FAU - Predolini, Federica
AU  - Predolini F
FAU - Bonazzoli, Elena
AU  - Bonazzoli E
FAU - Bussi, Beatrice
AU  - Bussi B
FAU - Stuhmer, Zachary
AU  - Stuhmer Z
FAU - Schwab, Carlton L
AU  - Schwab CL
FAU - English, Diana P
AU  - English DP
FAU - Ratner, Elena
AU  - Ratner E
FAU - Silasi, Dan-Arin
AU  - Silasi DA
FAU - Azodi, Masoud
AU  - Azodi M
FAU - Schwartz, Peter E
AU  - Schwartz PE
FAU - Rutherford, Thomas J
AU  - Rutherford TJ
FAU - Santin, Alessandro D
AU  - Santin AD
LA  - eng
GR  - U01 CA176067/CA/NCI NIH HHS/United States
GR  - U01 CA176067-01A1/CA/NCI NIH HHS/United States
GR  - R01 CA154460/CA/NCI NIH HHS/United States
GR  - CA-16359/CA/NCI NIH HHS/United States
GR  - P30 CA016359/CA/NCI NIH HHS/United States
GR  - R01 CA154460-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150211
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinazolinones)
RN  - 5092U85G58 (dacomitinib)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cystadenocarcinoma, Serous/*drug therapy/genetics/pathology
MH  - Female
MH  - Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Protein Kinase Inhibitors/*administration & dosage
MH  - Quinazolinones/*administration & dosage
MH  - Receptor, ErbB-2/antagonists & inhibitors/*genetics
MH  - Uterine Neoplasms/*drug therapy/genetics/pathology
PMC - PMC5573583
MID - NIHMS897860
COIS- Conflicts of interest: The authors report no conflicts of interest
EDAT- 2015/02/12 06:00
MHDA- 2015/10/27 06:00
PMCR- 2017/08/28
CRDT- 2015/02/12 06:00
PHST- 2014/12/17 00:00 [received]
PHST- 2015/02/03 00:00 [accepted]
PHST- 2015/02/12 06:00 [entrez]
PHST- 2015/02/12 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
PHST- 2017/08/28 00:00 [pmc-release]
AID - 10.1007/s13277-015-3218-4 [pii]
AID - 10.1007/s13277-015-3218-4 [doi]
PST - ppublish
SO  - Tumour Biol. 2015 Jul;36(7):5505-13. doi: 10.1007/s13277-015-3218-4. Epub 2015 
      Feb 11.