Abstract:
:EGFR is frequently overexpressed in head and neck squamous cell cancer (HNSCC). Cetuximab is a monoclonal antibody designed to interact with EGFR, block its activation, reduce the downstream signaling pathways and induce EGFR internalization. This study aims to investigate the role of the EGFR signaling pathway and EGFR internalization in a cetuximab-resistant cell line and to propose a new therapeutic strategy to optimize treatment of HNSCC. The HNSCC cell line, CAL33 was sensitive to gefitinib but resistant to cetuximab. Cetuximab induces an unexpected EGFR phosphorylation in CAL33 cells similarly to EGF but this EGFR activation does not trigger EGFR internalization/degradation, the process currently implicated in the response to cetuximab. Cetuximab inhibits ERK and AKT phosphorylation in cetuximab-sensitive A431 cells, whereas the level of AKT phosphorylation is unmodified in cetuximab-resistant cells. Interestingly, CAL33 cells harbor a PIK3CA mutation. The treatment of CAL33 cells with PI3K inhibitor and cetuximab restores the inhibition of AKT phosphorylation and induces growth inhibition. Our results indicate that EGFR internalization is impaired by cetuximab treatment in CAL33 cells and that the AKT pathway is a central element in cetuximab resistance. The combination of cetuximab with a PI3K inhibitor could be a good therapeutic option in PIK3CA-mutated HNSCC.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Rebucci M,Peixoto P,Dewitte A,Wattez N,De Nuncques MA,Rezvoy N,Vautravers-Dewas C,Buisine MP,Guerin E,Peyrat JP,Lartigau E,Lansiaux Asubject
Has Abstractpub_date
2011-01-01 00:00:00pages
189-200issue
1eissn
1019-6439issn
1791-2423journal_volume
38pub_type
杂志文章abstract::The development of colorectal cancer (CRC) is strongly correlated with the aberrant activation of multiple intracellular signaling transduction cascades including STAT3, ERK, JNK and p38 pathways which usually function redundantly. In addition, crosstalk between these pathways forms a complicated signaling network tha...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2040
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abstract::Retinoids, which include vitamin A (retinol) and its derivatives, have previously been investigated as potential chemopreventive and chemotherapeutic agents in bladder cancer. We examined mRNA expression of the retinoid receptors RARalpha, RARbeta2, RARgamma and RXRalpha, as well as two putative RARbeta2 target genes,...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
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journal_title:International journal of oncology
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doi:10.3892/ijo.2014.2519
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journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
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更新日期:2011-01-01 00:00:00
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::Family with sequence similarity 83 member A (FAM83A) has been recently observed to be upregulated in various types of cancer and hypothesized to be serve as an oncogene. The present study aimed to determine the functional roles and the underlying molecular mechanism of FAM83A in cervical cancer. The results demonstrat...
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pub_type: 杂志文章
doi:10.3892/ijo.2013.1971
更新日期:2013-08-01 00:00:00
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pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.4.627
更新日期:1993-10-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:1998-11-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.6.1103
更新日期:1993-12-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5163
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
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journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1021
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journal_title:International journal of oncology
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abstract::To establish a prostate cancer model expressing prostate-specific antigen (PSA) with metastatic potential, LNCaP or PC-3 cells were inoculated into the testis of SCID mice, resulting in a 100% rate of tumor formation. A significant increase in serum PSA was found in mice with LNCaP xenografts. Circulating tumor cells ...
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pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:2001-08-01 00:00:00