Abstract:
:Amplification of the HER-2 gene occurs in approximately 25% of breast cancers, causing up-regulation of key signaling pathways which control cell growth and survival. In breast cancer patients, HER-2 overexpression correlates with an aggressive phenotype and poor prognosis. HER-2, therefore, has become the focus of many anti-cancer therapeutic approaches. Trastuzumab (Herceptin), a humanized monoclonal antibody directed against the extracellular domain of HER-2, was the first FDA-approved HER-2-targeted therapy for the treatment of metastatic breast cancer. However, not all HER-2-overexpressing patients respond to trastuzumab and most that initially respond develop resistance within one year of treatment. Trastuzumab resistance has been studied in cell line models of resistance and several mechanisms of resistance have been proposed. More recent anti-HER-2 strategies involve targeting its tyrosine kinase domain; for example, lapatinib (Tykerb) is a dual HER-2 and EGFR tyrosine kinase inhibitor and has shown efficacy as a single agent and in combination with other therapeutics. A number of novel HER-2 antagonists are currently in preclinical or clinical development, including both monoclonal antibodies and small molecule inhibitors. Increased understanding of HER-2 signaling in breast cancer, and of response and resistance to HER-2 antagonists, will aid the development of strategies to overcome resistance to HER-2 targeted therapies.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Browne BC,O'Brien N,Duffy MJ,Crown J,O'Donovan Ndoi
10.2174/156800909788166484subject
Has Abstractpub_date
2009-05-01 00:00:00pages
419-38issue
3eissn
1568-0096issn
1873-5576journal_volume
9pub_type
杂志文章,评审abstract:BACKGROUND:Cathepsin D (CATD), one of the aspartyl endoproteinase involved in different physiological processes and signaling pathways, is accountable for metabolic breakdown of intracellular proteins, the activation of growth factors, hormones, and precursors of enzyme, the processing of antigens, enzyme inhibitors an...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666161229145115
更新日期:2017-01-01 00:00:00
abstract::Copper is a trace element which is tightly regulated in mammals and lower animals. Disruptions of copper homeostasis in humans are rare and they cause serious disorders such as Wilson's disease and Menke's disease. Copper plays an important role in promoting physiological and malignant angiogenesis. Formation of new b...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800905774574066
更新日期:2005-11-01 00:00:00
abstract::Prostate cancer is the most frequently diagnosed tumor in industrialized countries. Endocrine therapy, which is based on interference with androgen signaling is only palliative. Drugs used in prostate cancer therapy are luteinizing hormone releasing hormone (LHRH) agonists and antiandrogens. Application of LHRH agonis...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332925
更新日期:2004-08-01 00:00:00
abstract::Aberrant expression of the RON receptor tyrosine kinase contributes to breast cancer malignancy. Although clinical trials of RON targeting are underway, the intriguing issue is the diversity of RON expression as evident by cancer cells expressing different variants including oncogenic RON160. The current study determi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/15680096113139990038
更新日期:2013-07-01 00:00:00
abstract::The evolution of genomic research enabled the genetic and molecular profiling of breast cancer and revealed the profound complexity and heterogeneity of this disease. Subtypes of breast cancer characterized by mutations and/or amplifications of some proto-oncogenes are associated with an increased rate of recurrence a...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160603123014
更新日期:2017-01-01 00:00:00
abstract::Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781662284
更新日期:2007-09-01 00:00:00
abstract:BACKGROUND AND AIM:Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patient...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911793743600
更新日期:2011-01-01 00:00:00
abstract::Selection of treatment options for clinically localized prostate cancer is based on a host of factors including the patient's age, overall health status, potential complications, clinical tumor stage and Gleason score. It is widely acknowledged that androgen independent disease remains the main obstacle to improving t...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043481623
更新日期:2004-02-01 00:00:00
abstract::Sporadic colorectal cancer develops through a number of functional mutations. Key events are mutually exclusive mutations in BRAF or RAS oncogenes. Signatures for BRAF oncogene have been revealed in melanoma. In a previous study we have reported a molecular signature for HRAS and KRAS mutations in colorectal cell line...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800912802429364
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND:Improving poorly soluble drugs into druggability was a major problem faced by pharmaceutists. Nanosuspension can improve the druggability of insoluble drugs by improving the solubility, chemical stability and reducing the use of additives, which provided a new approach for the development and application of ...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009618666180629150927
更新日期:2019-01-01 00:00:00
abstract::Histone deacetylase inhibitors (HDACi) belong to a novel class of drugs able to act on the epigenome, indirectly remodeling the spatial conformation of the chromatin: by increasing histone acetylation these drugs ultimately promote the detachment of the DNA from the nucleosome octamer, therefore allowing the access of...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908784533508
更新日期:2008-06-01 00:00:00
abstract::Cell-penetrating peptides (CPPs) have been previously shown to be powerful transport vector tools for the delivery of a large variety of cargoes through the cell membrane, as well as other physiological membranes. And since they're relatively cell-, receptor- and energy-independent, CPPs have unique advantages in faci...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666150211104524
更新日期:2015-01-01 00:00:00
abstract::The peptidyl prolyl isomerase (Pin1) that induces cis-trans isomerization of the peptide bond involving serine/threonine-proline has recently been shown to regulate the activity of many phosphoproteins including the ones involved in damage response pathways. We investigated Pin1 as a potential target for enhancing the...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800911794519761
更新日期:2011-03-01 00:00:00
abstract::The anticancer properties of histone deacetylase inhibitors have been known for some time. However, it is only recently that the functional identities of the intracellular targets mediating the anticancer properties have started to be revealed. These targets appear to play significant roles in cell cycle control, apop...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023333818
更新日期:2002-12-01 00:00:00
abstract::Degradation of extracellular matrix is crucial for malignant tumor growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009053765799
更新日期:2005-05-01 00:00:00
abstract::CXCR4 is a chemokine receptor implicated in the metastatic process. The CXCR4 ligand, CXCL12, was shown to bind also the CXCR7 receptor, a recently deorphanized chemokine receptor whose signalling pathway and function are still controversial. This study was conducted to determine patients clinic-pathological factors a...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800910793605839
更新日期:2010-11-01 00:00:00
abstract::Mammalian target of rapamycin (mTOR) is a key protein kinase controlling signal transduction from various growth factors and upstream proteins to the level of mRNA translation and ribosome biogenesis, with pivotal regulatory effects on cell cycle progression, cellular proliferation and growth, autophagy and angiogenes...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791517172
更新日期:2010-08-01 00:00:00
abstract::Several subtypes of T cells are located in a tumor environment, each of which supplies their energy using different metabolic mechanisms. Since the cancer cells require high levels of glucose, the conditions of food poverty in the tumor environment can cause inactivation of immune cells, especially the T-effector cell...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009620666200720010647
更新日期:2020-01-01 00:00:00
abstract::One of the crucial reasons of breast cancer therapy failure is an impairment of mechanisms responsible for metabolism and cellular homeostasis, which makes it difficult to foresee the response to the treatment. Targeted therapy in breast cancer is dictated by the expression of specific molecules such as growth factor ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666171114143330
更新日期:2018-01-01 00:00:00
abstract::Targeted therapies focus on signaling pathways in cancer cells and other molecular processes involved in oncogenesis. Recent approaches affect the following major groups: the epidermal growth factor receptor (EGFR)-family, angiogenesis, the eicosanoid pathway, the PKC/ Ras/ MAPK pathway, the proteasome and inducers of...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906777441780
更新日期:2006-06-01 00:00:00
abstract::Polysialic acid (polySia) is a carbohydrate polymer critical for neuronal cell migration and axon pathfinding in embryonic development. Besides brain regions requiring persistent neuronal plasticity, polySia is essentially absent from the adult body. However, polySia is aberrantly re-expressed on many tumours, where i...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912803251225
更新日期:2012-10-01 00:00:00
abstract::Gastrointestinal (GI) tumors are among the leading cause of death in cancer patients worldwide. Particularly, gastric cancer (GC) is the third cause of cancer deaths, whereas esophageal neoplasm is the eighth leading most common cancer worldwide and its incidence, especially adenocarcinoma type, is continuously increa...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170208162058
更新日期:2018-01-01 00:00:00
abstract::The Jun oncoprotein is a major component of the transcription factor complex AP-1, which regulates the expression of multiple genes essential for cell proliferation, differentiation and apoptosis. Constitutive activation of endogenous AP-1 is required for tumor formation in avian and mammalian cell transformation syst...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033333781
更新日期:2003-02-01 00:00:00
abstract::Cyclooxygenase-2 (COX-2) is a critical enzyme implicated in chronic inflammation-associated cancer development. Our studies have shown that the exposure of Beas-2B cells, a human bronchial epithelial cell line, to lung carcinogenic nickel compounds results in increased COX-2 expression. However, the signaling pathways...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800911795656001
更新日期:2011-06-01 00:00:00
abstract::Despite remarkable progress that has been made in the recent years in the treatment of gastrointestinal tumors, in particular colorectal cancer, the prognosis of pancreatic cancer remains dismal. Five years after diagnosis almost all patients have died. At early stages of the disease surgery is the only modality to ac...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911796191079
更新日期:2011-07-01 00:00:00
abstract::Breast cancer is one of the most common malignancies among women, representing nearly 30% of newly diagnosed cancers every year. Till date, various therapeutic interventions, including surgery, chemotherapy, hormonal therapy, and radiotherapy are available and are known to cause a significant decline in the overall mo...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666141229152256
更新日期:2015-01-01 00:00:00
abstract::Glioma-associated oncogenes (GLIs) are zinc finger protein family members and downstream regulatory factors of the classic Hedgehog (Hh) signaling pathway. GLI proteins influence the growth and development of organisms and aid in tissue repair. However, aberrant expression of the GLI family member GLI1 promotes carcin...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666171129223533
更新日期:2018-01-01 00:00:00
abstract::Although the imatinib based therapy of chronic myeloid leukemia (CML) represents a triumph of medicine, not all patients with CML benefit from this drug due to the development of resistance and intolerance. The interruption of imatinib treatment is often followed by clinical relapse, suggesting a failure in the killin...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113139990083
更新日期:2013-09-01 00:00:00
abstract::Drugs that target the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) pathways have revolutionized the treatment of patients with metastatic renal cell cancer (RCC). Patients with clear cell RCC often have mutations or silencing of the von Hippel Lindau gene leading to an accumulati...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908786733450
更新日期:2008-12-01 00:00:00
abstract::(5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of the Cp2TiCl2 catalyst giving 2,5-dialkylydenemagnesacyclopentane in 86% yield. The acid hyd...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009615666150506093155
更新日期:2015-01-01 00:00:00