Abstract:
:In light of a detailed characterization of genetic aberrations in cancer, nucleic acid targeting represents an attractive therapeutic approach with significant translational potential. Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer deaths worldwide with stagnant 5-year survival rates. Advances in conventional treatment have done little to improve survival and combined chemoradiation is associated with significant adverse effects. Recent reports have characterized the genetic alterations in HNSCC and demonstrated that mutations confer resistance to conventional and molecular targeted therapies. The ability to use specific nucleic acid sequences to inhibit cancer-associated genes including non-druggable targets facilitates personalized medicine approaches with less adverse effects. Additionally, advances in drug delivery mechanisms have increased the transfection efficiency aiding in greater therapeutic responses. Given these advances, the stage has been set to translate the information garnered from genomic studies into personalized treatment strategies. Genes involved in the tumor protein 53 and epidermal growth factor receptor pathways have been extensively investigated and many promising preclinical studies have shown tumor inhibition through genetic modulation. We, and others, have demonstrated that targeting oncogene expression with gene therapy approaches is feasible in patients. Other methods such as RNA interference have proven to be effective and are potential candidates for clinical studies. This review summarizes the major advances in sequence-specific gene modulation in the preclinical setting and in clinical trials in head and neck cancer patients.
journal_name
Oncogenejournal_title
Oncogeneauthors
Parsel SM,Grandis JR,Thomas SMdoi
10.1038/onc.2015.424subject
Has Abstractpub_date
2016-06-23 00:00:00pages
3217-26issue
25eissn
0950-9232issn
1476-5594pii
onc2015424journal_volume
35pub_type
杂志文章,评审相关文献
ONCOGENE文献大全abstract::Waldenström macroglobulinemia (WM) is a proliferative disorder of IgM-secreting, lymphoplasmacytoid cells that inhabit the lymph nodes and bone marrow. The disease carries a high prevalence of activating mutations in MyD88 (91%) and CXCR4 (28%). Because signaling through these pathways leads to Bcl-xL induction, we ex...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.103
更新日期:2016-01-28 00:00:00
abstract::Wild-type (wt) p53 acts as a tumor suppressor, while certain mutant type (mt) p53 may exhibit 'oncogenic' function. We have recently demonstrated that human papillomavirus type 18 (HPV-18) E6 can partially overcome the growth-suppressive effects of wt p53, but it remains unclear what role p53 plays in cervical carcino...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Non-small cell lung cancer (NSCLC) accounts for ∼80% of all lung cancers. Although some advances in lung cancer therapy have been made, patient survival is still quite poor. Two microRNAs, miR-221 and miR-222, upregulated by the MET proto-oncogene, have been already described to enhance cell survival and to induce TNF...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.260
更新日期:2012-02-02 00:00:00
abstract::Previous reports have demonstrated that E7 is the major transforming gene of HPV-16 and that continued expression of the gene is required to maintain the transformed phenotype of primary baby rat kidney cells transformed by HPV-16 E7 and EJ-ras. To investigate the point of action of E7 in the cell cycle we have utilis...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways impl...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2010.13
更新日期:2010-04-01 00:00:00
abstract::SMARCB1 (Snf5/Ini1/Baf47) is a potent tumor suppressor, the loss of which serves as the diagnostic feature in malignant rhabdoid tumors (MRT) and atypical teratoid/rhabdoid tumors (AT/RT), two highly aggressive forms of pediatric neoplasms. SMARCB1 is a core subunit of Swi/Snf chromatin remodeling complexes, and loss ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.261
更新日期:2014-06-05 00:00:00
abstract::A variety of factors cooperate to regulate neovessel formation and persistence. Proangiogenic growth factors have remained an area of intense interest due to their capacity to promote endothelial cell (EC) proliferation and to initiate the angiogenic program. These growth factors are associated with increased cell sur...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1207110
更新日期:2003-12-08 00:00:00
abstract::Basic helix-loop-helix (bHLH) transcription factors play a pivotal role in the regulation of tumorigenesis, and also in a wide range of other developmental processes in diverse species from yeast to humans. Here we demonstrate for the first time that Ret finger protein (RFP), a member of the TRIM family of proteins in...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208828
更新日期:2005-10-13 00:00:00
abstract::Diffuse intrinsic pontine glioma (or DIPG) are pediatric high-grade gliomas associated with a dismal prognosis. They harbor specific substitution in histone H3 at position K27 that induces major epigenetic dysregulations. Most clinical trials failed so far to increase survival, and radiotherapy remains the most effici...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0884-5
更新日期:2019-09-01 00:00:00
abstract::Cell to cell communication is vital throughout the development of multicellular organisms and during adult homeostasis. One way in which communication is achieved is through the secretion of signaling molecules that are received by neighboring responding cells. Wnt ligands comprise a large family of secreted, hydropho...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210053
更新日期:2006-12-04 00:00:00
abstract::Ras genes, frequently mutated in human tumors, promote malignant transformation. Ras transformation requires membrane anchorage, which is promoted by Ras farnesylcysteine carboxymethylester and by a second signal. Previously we showed that the farnesylcysteine mimetic, farnesylthiosalicylic acid (FTS) disrupts Ras mem...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204950
更新日期:2001-11-08 00:00:00
abstract::The oncogene EWS-FLI1 encodes a chimeric transcription factor expressed in Ewing's sarcoma family tumors (ESFTs). EWS-FLI1 target gene expression is thought to drive ESFT pathogenesis and, therefore, inhibition of EWS-FLI1 activity holds high therapeutic promise. As the activity of many transcription factors is regula...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.484
更新日期:2009-03-05 00:00:00
abstract::P53 wild-type and p53-null or mutant cells undergo a G(2)-phase cell-cycle arrest in response to ionizing radiation (IR). In this study we examined the effect of heat-shock protein 90 (HSP90) inhibitor, geldanamycin (GA), on IR-induced G(2) arrest in human colon adenocarcinoma cells with different p53 status. We show ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.172
更新日期:2008-09-18 00:00:00
abstract::Deletions involving chromosome 9 occur in more than 50% of human bladder cancers of all grades and stages. Most involve loss of the whole chromosome or of an entire chromosome arm but some small deletions are found which can be used to define critical regions which may contain tumour suppressor genes. We have localize...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202854
更新日期:1999-04-22 00:00:00
abstract::While advances in laboratory automation has dramatically increased throughout of compound screening efforts, development of robust cell-based assays in relevant disease models remain resource-intensive and time-consuming, presenting a bottleneck to drug discovery campaigns. To address this issue, we present a modified...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0274-4
更新日期:2018-08-01 00:00:00
abstract::Transgenic mice expressing the c-Myc oncogene driven by woodchuck hepatitis virus (WHV) regulatory sequences develop hepatocellular carcinoma with a high frequency. To investigate genetic lesions that cooperate with Myc in liver carcinogenesis, we conducted a genome-wide scan for loss of heterozygosity (LOH) and mutat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205208
更新日期:2002-02-28 00:00:00
abstract::Checkpoint protein Chk1 has been identified as an Hsp90 client. Treatment with 100 nM geldanamycin (GM) for 24 h markedly reduced the Chk1 amount in Jurkat and ML-1 leukemia cell lines. Because Chk1 plays a central role in G2 checkpoint, we added GM to G2-arrested Jurkat and HL-60 cells pretreated with 50 nM doxorubic...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210978
更新日期:2008-05-15 00:00:00
abstract::As apoptosis defects limit efficacy of anticancer agents, autophagy has been proposed as a novel strategy for radiotherapy enhancement. We previously showed that caspase-3/7 inhibition induces autophagy and promotes radiosensitivity in vitro and in vivo. Therefore, we further investigated the mechanism by which radiat...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.74
更新日期:2010-06-03 00:00:00
abstract::E1A of human adenovirus type 5 (Ad5) encodes proteins of 289 and 243 residues (289R and 243R) which differ only by the 46 amino acid CR3 region known to activate expression of certain cellular and early viral genes. E1A proteins also induce DNA synthesis and cell transformation, but as well can stimulate apoptosis. Tw...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-08-03 00:00:00
abstract::We previously reported the development of a src-specific tumor regression system in chickens in which preinfection with rASV1702, a mutant of Rous sarcoma virus (RSV) encoding non-myristylated src product with a novel N-terminal domain, results in the immune suppression of challenge tumors induced by RSV. In order to ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor gene with its expression downregulated in multiple cancer types. The role of DAB2 in lung tumorigenesis, however, is not fully characterized, and the mechanisms of DAB2 dysregulation in lung cancer are not defined. Here we show that low D...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.381
更新日期:2014-08-21 00:00:00
abstract::Glypican-3 (GPC3) is a membrane-bound heparan sulfate proteoglycan that is mutated in the Simpson-Golabi-Behmel syndrome. This is an X-linked condition characterized by overgrowth, and various visceral and skeletal dysmorphisms. The phenotype of the Simpson-Golabi-Behmel syndrome patients and GPC3-deficient mice, as w...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204925
更新日期:2001-11-01 00:00:00
abstract::The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201939
更新日期:1998-07-16 00:00:00
abstract::Obesity is a highly prevalent and modifiable breast cancer risk factor. While the role of obesity in fueling breast cancer progression is well established, the mechanisms linking obesity to breast cancer initiation are poorly understood. A hallmark of breast cancer initiation is the disruption of apical polarity in ma...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0687-8
更新日期:2019-05-01 00:00:00
abstract::Overexpression of the nuclear phosphoprotein p53 has been detected in many different transformed human cell lines and primary adult tumors. Elevated steady-state levels of p53 appear to be the result of an increase in the stability of the protein and, in adult cancers, high levels of the protein are associated with mu...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Alterations affecting the epidermal growth factor (EGF)/transforming growth factor alpha (TGF alpha)-responsive mitogenic pathway are frequently detected in malignancies. In particular, the EGF-receptor (EGFR) molecule has been found overexpressed in a number of human tumors, and TGF alpha is produced by a large array...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formati...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.512
更新日期:2017-07-06 00:00:00
abstract::Gene silencing associated with aberrant methylation of promoter region CpG islands is one mechanism in which tumor suppressor genes are inactivated in human cancers. Recently, we identified a novel gene, Target of Methylation-associated Silencing-1 (TMS1) (also called ASC), which is aberrantly methylated and silenced ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206430
更新日期:2003-05-29 00:00:00
abstract::Apoptosis ligand 2 tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL) belongs to a small subset of proapoptotic protein ligands in the TNF superfamily. This subset, which also includes Fas ligand and TNF-alpha, can activate the extrinsic apoptotic cell death pathway on binding to cognate death...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2010.221
更新日期:2010-08-26 00:00:00
abstract::Recent years have seen a great expansion in our understandings of how silent mutations can drive a disease and that mRNAs are not only mere messengers between the genome and the encoded proteins but also encompass regulatory activities. This review focuses on how silent mutations within open reading frames can affect ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/onc.2015.454
更新日期:2016-07-21 00:00:00