PMID- 25725588
OWN - NLM
STAT- MEDLINE
DCOM- 20151230
LR  - 20220413
IS  - 1879-0593 (Electronic)
IS  - 1368-8375 (Linking)
VI  - 51
IP  - 5
DP  - 2015 May
TI  - Mechanisms of and therapeutic approaches for overcoming resistance to epidermal 
      growth factor receptor (EGFR)-targeted therapy in squamous cell carcinoma of the 
      head and neck (SCCHN).
PG  - 399-408
LID - S1368-8375(15)00030-5 [pii]
LID - 10.1016/j.oraloncology.2015.01.018 [doi]
AB  - The majority of squamous cell carcinoma of the head and neck (SCCHN) overexpress 
      epidermal growth factor receptor (EGFR), which has been associated with poor 
      treatment response and survival. However, only modest success has been achieved 
      with the use of single agents that target EGFR, possibly due to primary and 
      acquired resistance. This review will discuss key mechanisms of and therapeutic 
      approaches to overcoming resistance to EGFR-targeted therapy in SCCHN. Recent 
      preclinical and clinical investigations have demonstrated that other ErbB family 
      receptors (eg, HER2 and HER3) and other horizontal resistance mechanisms, as well 
      as activation of downstream signaling pathways, epigenetic events, and nuclear 
      EGFR, are possible mediators of resistance to anti-EGFR therapeutics. Key 
      downstream pathways that may be implicated in EGFR resistance include 
      phosphatidylinositol-3-kinase/protein kinase B, vascular endothelial growth 
      factor (VEGF), and mammalian target of rapamycin (mTOR). Multiple agents that 
      target EGFR and other ErbB family members (ie, lapatinib, afatinib, and 
      dacomitinib), as well as combination therapies that target EGFR and selected 
      other pathways (eg, VEGF, mTOR, and c-Met) are being investigated clinically. In 
      addition, several phase II and III trials continue to investigate strategies to 
      enhance the efficacy of EGFR-targeted therapy in SCCHN.
CI  - Copyright (c) 2015 Elsevier Ltd. All rights reserved.
FAU - Price, Katharine A R
AU  - Price KA
AD  - Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA. Electronic 
      address: price.katharine@mayo.edu.
FAU - Cohen, Ezra E W
AU  - Cohen EE
AD  - Section of Hematology/Oncology, Department of Medicine, University of Chicago, 
      Chicago, IL, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150226
PL  - England
TA  - Oral Oncol
JT  - Oral oncology
JID - 9709118
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Carcinoma, Squamous Cell/*drug therapy
MH  - Drug Resistance, Neoplasm
MH  - ErbB Receptors/*antagonists & inhibitors
MH  - Head and Neck Neoplasms/*drug therapy
MH  - Humans
OTO - NOTNLM
OT  - Clinical trial
OT  - Drug resistance
OT  - Epidermal growth factor receptor
OT  - HER2
OT  - HER3
OT  - Molecular targeted therapy
OT  - Squamous cell carcinoma of the head and neck
EDAT- 2015/03/03 06:00
MHDA- 2015/12/31 06:00
CRDT- 2015/03/02 06:00
PHST- 2014/04/22 00:00 [received]
PHST- 2015/01/19 00:00 [revised]
PHST- 2015/01/28 00:00 [accepted]
PHST- 2015/03/02 06:00 [entrez]
PHST- 2015/03/03 06:00 [pubmed]
PHST- 2015/12/31 06:00 [medline]
AID - S1368-8375(15)00030-5 [pii]
AID - 10.1016/j.oraloncology.2015.01.018 [doi]
PST - ppublish
SO  - Oral Oncol. 2015 May;51(5):399-408. doi: 10.1016/j.oraloncology.2015.01.018. Epub 
      2015 Feb 26.