Abstract:
:The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers. Cetuximab is an anti-EGFR monoclonal antibody that has been approved for use in oncology. Despite clinical success the majority of patients do not respond to cetuximab and those who initially respond frequently acquire resistance. To understand how tumor cells acquire resistance to cetuximab we developed a model of resistance using the non-small cell lung cancer line NCI-H226. We found that cetuximab-resistant (Ctx (R) ) clones manifested strong activation of EGFR, PI3K/AKT and MAPK. To investigate the role of AKT signaling in cetuximab resistance we analyzed the activation of the AKT pathway effector molecules using a human AKT phospho-antibody array. Strong activation was observed in Ctx (R) clones for several key AKT substrates including c-jun, GSK3β, eIF4E, rpS6, IKKα, IRS-1 and Raf1. Inhibition of AKT signaling by siAKT1/2 or by the allosteric AKT inhibitor MK-2206 resulted in robust inhibition of cell proliferation in all Ctx (R) clones. Moreover, the combinational treatment of cetuximab and MK-2206 resulted in further decreases in proliferation than either drug alone. This combinatorial treatment resulted in decreased activity of both AKT and MAPK thus highlighting the importance of simultaneous pathway inhibition to maximally affect the growth of Ctx (R) cells. Collectively, our findings demonstrate that AKT activation is an important pathway in acquired resistance to cetuximab and suggests that combinatorial therapy directed at both the AKT and EGFR/MAPK pathways may be beneficial in this setting.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Iida M,Brand TM,Campbell DA,Starr MM,Luthar N,Traynor AM,Wheeler DLdoi
10.4161/cbt.24342subject
Has Abstractpub_date
2013-06-01 00:00:00pages
481-91issue
6eissn
1538-4047issn
1555-8576pii
24342journal_volume
14pub_type
杂志文章abstract::With the increasing interest in development of cytostatic anticancer drugs, the randomized discontinuation trial (RDT) design has been proved to be useful in the evaluation of their clinical activity. In the June 1, 2006 issue of the Journal of Clinical Oncology, a study by Ratain et al. uses RDT in a phase-II placebo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,随机对照试验
doi:10.4161/cbt.5.10.3290
更新日期:2006-10-01 00:00:00
abstract::Retinoids are used in leukemia therapy and chemoprevention of cancers. Treatment of MCF-7 breast carcinoma cells with low doses of retinoids induces gradual proliferation arrest with phenotypic markers of senescence. cDNA microarray hybridization and reverse transcription-polymerase chain reaction analysis showed that...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.1.1.35
更新日期:2002-01-01 00:00:00
abstract::Angiogenesis inhibitors belong to a new class of drugs. Many of these drugs are in clinical trials to treat cancer, while others have recently received FDA approval. However, angiogenesis inhibitors operate by different mechanisms than conventional cytotoxic chemotherapies, and require different guidelines for their o...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:
更新日期:2003-07-01 00:00:00
abstract::The alterative reading frame (ARF) protein is unique in its capacity to interact with Mdm2 thus facilitating p53-dependent cell cycle arrest and apoptosis. ARF also acts in a p53-independent manner in which it binds to Myc and interferes with transcriptional activation by Myc thereby inhibiting Myc-induced cell prolif...
journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.5.6.2939
更新日期:2006-06-01 00:00:00
abstract::Fluids of body cavities result in a series of pathophysiological events associated with non-malignant and malignant conditions that lead to the formation of exudative effusion. Diagnosis of effusion from the patients is frequently troublesome for the cytologist because of the differentiation and biological behavior of...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.2.1573
更新日期:2005-02-01 00:00:00
abstract::DNA methylation at the 5 position of cytosine (5-mC) has emerged as a key epigenetic marker that plays essential roles in various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family proteins, which is now widely recognized as the ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.27144
更新日期:2014-01-01 00:00:00
abstract::As a kinase at the crossroads of numerous metabolic and cell growth signaling pathways, glycogen synthase kinase-3 beta (GSK-3β) is a highly desirable therapeutic target in cancer. Despite its involvement in pathways associated with the pathogenesis of several malignancies, no selective GSK-3β inhibitor has been appro...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2019.1595283
更新日期:2019-01-01 00:00:00
abstract::Exosomes released from cancer cells support metastasis and growth of recipient cells and increase their resistance to chemotherapy. Therapeutic targeting of exosomes is a promising area in cancer research. Our aim is to test the effect of the mast cell stabilizer ketotifen on exosomes release from cancer cells and how...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1394544
更新日期:2018-01-02 00:00:00
abstract::Tumors with identical phenotype can have markedly different biologic behavior. The differentiation between hemangioblastoma, a benign vascular brain tumor, and renal cell carcinoma (RCC), a malignant tumor that can metastasize to the brain, is a well-known pathological quandary. We report a 59-year-old female with von...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.3.3673
更新日期:2007-03-01 00:00:00
abstract::Any drug selects for drug resistance. But super-antagonistic drug combinations can select for drug sensitivity. This has important application not only for antibacterial therapy but also for cancer therapy: to control cancer with lesser side effects and to eliminate drug-resistant cancer cells, while sparing sensitive...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.7.4340
更新日期:2007-07-01 00:00:00
abstract::Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1323597
更新日期:2017-07-03 00:00:00
abstract::A greater understanding of the molecular basis of breast cancer metastasis will lead to identification of novel therapeutic targets and better treatments. Rap1B is a small GTPase that suppresses the metastasis of breast cancer cells by increasing cell-cell adhesion. In breast cancer, a decrease in Rap1B prenylation an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1070988
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:IL-24 (interleukin-24) is a promising, multi-functional anti-cancer agent able to selectively induce tumor cell apoptosis while sparing normal cells. Additionally, IL-24 can enhance the immune response to tumors and suppress tumor angiogenesis. In this study, we introduced IL-24 into the oncolytic adenovirus...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.3.12308
更新日期:2010-08-01 00:00:00
abstract::Breast cancer is one of the most commonly diagnosed malignancies in women. Despite the remarkable success of mammography screening and use of adjuvant systemic therapy, it is estimated that approximately 200,000 new diagnoses will be made this year and 40,000 deaths will occur due to this disease (American Cancer Soci...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.9.17677
更新日期:2011-11-01 00:00:00
abstract::Chronic myeloid leukemia (CML) progresses from a chronic phase to a deadly blast crisis phase. While it is known that BCR-ABL initiates the disease and that secondary molecular and genetic abnormalities likely contribute to progression of the disease to blast crisis, details regarding the mechanism(s) of blast phase p...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.10.10.14010
更新日期:2010-11-15 00:00:00
abstract::For years, the growth inhibitory effects of the tumor suppressor p53 were thought to be antagonized predominantly by the ubiquitin ligase, MDM2. It has long been established that MDM2 physically associates with p53 and targets this tumor suppressor for proteasomal degradation. In light of recent findings, it now appea...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.8.1068
更新日期:2004-08-01 00:00:00
abstract::The present studies sought to further understand how the anti-folate pemetrexed and the multi-kinase inhibitor sorafenib interact to kill tumor cells. Sorafenib activated SRC, and via SRC the drug combination activated ERK1/2. Expression of dominant negative SRC or dominant negative MEK1 abolished drug-induced ERK1/2 ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20562
更新日期:2012-07-01 00:00:00
abstract::We previously reported that the mutant virus of HSV (mtHSV) mediated tumor therapy was efficacious in Balb/c and nude mice. However, it is significant to know whether mtHSV works in HSV-1 tumor seropositive individuals because many patients with HSV-1 seropositivity have been found in clinical trial. Here we asked whe...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.5.3953
更新日期:2007-05-01 00:00:00
abstract:BACKGROUND:Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2017.1281495
更新日期:2017-03-04 00:00:00
abstract:BACKGROUND:Unlike papillary thyroid cancer (PTC), anaplastic thyroid carcinoma (ATC) is extremely aggressive and rapidly lethal without effective therapies. However, the differences of master regulators and regulatory networks between PTC and ATC remain unclear. Methods: Three representative datasets comprising 32 ATC,...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1803009
更新日期:2020-09-01 00:00:00
abstract::Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in pros...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1078023
更新日期:2015-01-01 00:00:00
abstract::Long standing chronic pancreatitis is a risk factor for developing pancreatic cancer. Inheritance of polymorphisms in SPINK1 and CFTR are associated with an increased risk of developing pancreatitis. The aim of this study was to determine if patients who carry polymorphisms in SPINK1 and CFTR are at increased risk of ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
abstract::The screening for BRAF V600E mutation is employed in clinical practice for its prognostic and potentially predictive role in patients with metastatic colorectal carcinoma (mCRC). Little information is available on the sensitivity and specificity of the testing methods to detect this mutation in CRC. By using serial di...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1195048
更新日期:2016-08-02 00:00:00
abstract::Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1345393
更新日期:2017-12-02 00:00:00
abstract::Male germ cell tumors (GCTs) are a model for a curable solid tumor. GCTs can differentiate into mature teratomas. Embryonal carcinomas (ECs) represent the stem cell compartment of GCTs and are the malignant counterpart to embryonic stem (ES) cells. GCTs and EC cells are useful to investigate differentiation therapy an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.27821
更新日期:2014-04-01 00:00:00
abstract::Discovering drugs has never been an easy task. Traditionally, this task has exclusively been undertaken by large pharmaceutical companies that recovered their high research and development costs by selling expensive medications. Despite the huge amount of time and effort devoted towards drug discovery over the last de...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.2.4.448
更新日期:2003-07-01 00:00:00
abstract::The pediatric solid tumor neuroblastoma (NB) often depends on the anti-apoptotic protein, Mcl(-)1, for survival through Mcl(-)1 sequestration of pro-apoptotic Bim. High affinity Mcl(-)1 inhibitors currently do not exist such that novel methods to inhibit Mcl(-)1 clinically are in high demand. Receptor tyrosine kinases...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2014.1002333
更新日期:2015-01-01 00:00:00
abstract::Arsenic trioxide (As2O3) induces apoptosis in certain types of cancer cells. But the detailed mechanisms of As2O3 efficacy are not completely known. Here we demonstrate that As2O3 has a therapeutic effect on cervical cancer in vitro and in vivo. We investigated the As2O3-induced apoptosis in various cervical cancer ce...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.4.3887
更新日期:2007-04-01 00:00:00
abstract::Adenoid cystic cancers (ACC) in the head and neck are rare yet present a clinical dilemma. Although 5-y survivals are excellent, they have a propensity for late recurrences. Most of these cancers are initially treated with surgery followed by radiation. When recurrences happen, treatment options are limited both by th...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.20.9596
更新日期:2009-10-01 00:00:00
abstract::The Forkhead Box transcription factor FoxM1 regulates expression of genes that promote cell cycle progression, and it plays essential roles in the development of liver, lung, prostate and colorectal tumors. Thiazolidinediones (TZDs) activate the peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activa...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.12.11710
更新日期:2010-06-15 00:00:00