Abstract:
:Constitutive activation of the EGFR/RAS/PI3K cell-signaling pathway that may occur through molecular aberrations in core pathway components occurs in many solid tumours, including colorectal cancer(CRC), non-small-cell lung cancer(NSCLC) and breast cancer. Predictive biomarkers of response to therapeutics targeting this pathway are necessary to select patients more likely to respond, and importantly, to avoid treating patients likely to suffer a worse outcome with therapy compared to standard of care. Determination of EGFR by immunohistochemistry(IHC) is not strongly predictive of response to EGFR-targeted therapy in CRC and NSCLC. EGFR gene mutations in the tyrosine kinase(TK) binding domain are predictive of response to EGFR tyrosine kinase inhibitors(TKIs) in NSCLC, and the acquisition of a point mutation in a gene encoding an amino acid in an adjacent area, T790M, is predictive of resistance. However, novel irreversible EGFR inhibitors such as BIBW-2992 and HKI-272 may retain activity in tumours with T790M mutations. It is well established in CRC that mutations in KRAS are predictive of resistance to EGFR pathway inhibition, and may predict for a poorer outcome with therapy. Other potentially useful biomarkers of resistance to EGFR-targeted therapy in the process of clinical validation include mutations in BRAF, PTEN loss and PI3KCA mutations, nuclear factor-kappa beta(NF-Κβ) pathway activity, and expression of alternative EGFR ligands. Functional genomics elucidation of drug resistance pathways using RNA interference (RNAi) techniques may provide novel therapeutic approaches in disease resistant to EGFR pathway targeting and accelerate predictive biomarker development.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Barton S,Starling N,Swanton Cdoi
10.2174/156800910793357925subject
Has Abstractpub_date
2010-12-01 00:00:00pages
799-812issue
8eissn
1568-0096issn
1873-5576pii
EPub-Abstract-CCDT-68journal_volume
10pub_type
杂志文章,评审abstract::Platinum-based chemotherapeutics are the mainstay of treatment of a range of tumors achieving high response rates but limited in the course of disease by appearance of drug resistance. Tumor cells respond with reduced uptake and increased intracellular inactivation of the drugs, as well as increased DNA repair and gen...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113136660109
更新日期:2014-01-01 00:00:00
abstract::Cancer drug therapy is undergoing a major transition from the previous pregenomic cytotoxic era to the new postgenomic era. Future mechanism-based therapeutic agents will increasingly be designed to act on molecular targets that are causally involved in the malignant progression of human cancers. Such agents are predi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009013334269
更新日期:2001-05-01 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::Pokemon gene has crucial but versatile functions in cell differentiation, proliferation and tumorigenesis. It is a master regulator of the ARF-HDM2-p53 and Rb-E2F pathways. The facts that the expression of Pokemon is essential for tumor formation and many kinds of tumors over-express the Pokemon gene make it an attrac...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800910793357907
更新日期:2010-12-01 00:00:00
abstract::Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of normal as well as oncogenic proteins. These chaperones thereby prevent the formation of protein aggregates. HSPs are often overexpressed in human malignancies, including AML. HSP90 is the main chaperon required for the stabi...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789271486
更新日期:2009-09-01 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
abstract::The potential clinical applications of the prototype first-in-class Hsp90 inhibitor 17AAG and other emerging Hsp90 drugs are very exciting. Rigorously planned and executed clinical trials, incorporating measurement of appropriate biomarkers and pharmocodynamic endpoints are critical for selecting the optimal dose and ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009033481813
更新日期:2003-10-01 00:00:00
abstract::Angiogenesis is a key factor in the carcinogenesis process. In oncological practice, angiogenesis inhibition, mainly through the blockade of the VEGF family and its receptors, has been robustly demonstrated to produce clinical benefits and, in specific disease subsets such as colorectal cancer, to extend the overall s...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912800190929
更新日期:2012-05-01 00:00:00
abstract::Head and neck cancer, the sixth most common type of cancer worldwide, is associated with a dismal prognosis that has minimally improved during the last few decades. Future advances in the treatment and prognosis of this fatal disease largely rely upon a better understanding of the molecular events that underlie tumor ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043332736
更新日期:2004-12-01 00:00:00
abstract::Castration-resistant prostate cancer remains incurable and a major cause of mortality worldwide. The absence of effective therapeutic approaches for advanced prostate cancer has led to an intensive search for novel treatments. Emerging nanomedical approaches have shown promising results, in vitro and in vivo, in impro...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911797264770
更新日期:2011-10-01 00:00:00
abstract::Recent publications on the molecular characterization of malignant glioma have had profound impact on the appreciation of tumoral heterogeneity within and between patients. Both these phenomena are implicated in the variability in clinical outcome between patients, as well as the inevitable recurrence of these tumors ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666160813191809
更新日期:2017-01-01 00:00:00
abstract::An apparent low prevalence of cancer in hypertensive patients receiving angiotensin converting enzyme inhibitors is reported; however, the molecular mechanisms have not been elucidated. Angiotensin-II (Ang-II) is well known to be associated with hypertension, as a main peptide of the renin-angiotensin system, and its ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009054629663
更新日期:2005-08-01 00:00:00
abstract:BACKGROUND:Intestinal β-glucuronidase enzyme has a significant importance in colorectal carcinogenesis. Specific inhibition of the enzyme helps prevent immune reactivation of the glucuronide- carcinogens, thus protecting the intestine from ROS (Reactive Oxidative Species) mediatedcarcinogenesis. OBJECTIVES:Advancement...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009619666190320102238
更新日期:2019-01-01 00:00:00
abstract::Though modern available cancer therapies are effective, they possess major adverse effects, causing non-compliance to patients. Furthermore, the majority of the polymeric-based medication platforms are certainly not universally acceptable, due to their several restrictions. With this juxtaposition, lipid-based medicat...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009620666200115160805
更新日期:2020-01-01 00:00:00
abstract::Despite advances in multidisciplinary approaches, the prognosis for most patients with malignant gliomas is poor. Malignant gliomas are highly vascularized tumors with elevated expression of vascular endothelial growth factor (VEGF), an important mediator of angiogenesis. Recent studies of bevacizumab, an anti-VEGF mo...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800912799277584
更新日期:2012-03-01 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::Following the discovery that defective retinoid signaling directly contributes to tumorigenesis, and, that retinoids have an anti-cancer effect in vitro and in vivo, retinoids have become part of the routine care in children with neuroblastoma at the stage of minimal residual disease. However, many patients still rela...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800911796798968
更新日期:2011-09-01 00:00:00
abstract::One of the older and most validated cancer treatments is endocrine therapy. Some tumors are dependent on hormone stimulation for growth, and therefore therapeutic interventions aiming to deprive the cells of the hormone are feasible and have been successful. Tumor growth also depends in some cases on growth factors, s...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907780618310
更新日期:2007-05-01 00:00:00
abstract::Bisphosphonates are the standard of care for preventing skeletal morbidity and treating hypercalcemia of malignancy in patients with bone metastases. Zoledronic acid (intravenous; 4 mg monthly) is approved to prevent skeletal-related events (SREs) in patients with bone metastases from several tumor types, and can impr...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800909789760267
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Epidermal growth factor receptor (EGFR) is a well-recognised drug target exploited for treating non-small cell lung cancer (NSCLC). Gefitinib and erlotinib are first generation clinically employed inhibitors used against EGFR activating mutants. However, during course of treatment these inhibitors become ine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170330112842
更新日期:2017-01-01 00:00:00
abstract::There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids i...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009614666140122160515
更新日期:2014-01-01 00:00:00
abstract::Targets for cancer therapy are conventionally selected by identification of molecules acting downstream of established tumour suppressors and oncoproteins, such as p53, c-Myc and Ras. However, the forward genetics approach provides an alternative, conceptually distinct, strategy for identifying target molecules de nov...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:
更新日期:2013-01-01 00:00:00
abstract::The resistance of tumors to a number of structurally and functionally unrelated chemotherapeutic drugs has been a major obstacle for successful cancer chemotherapy. An important mechanism leading to multidrug resistance (MDR) is the overexpression of the 170 kDa P-glycoprotein (P-gp), which is a member of the ATP-bind...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/15680096113139990082
更新日期:2013-10-01 00:00:00
abstract:BACKGROUND:MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability. METHODS:In this research, we successfully constructed 11-mercaptoundecanoic acid modified go...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009618666181016144855
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Oncolytic viruses (OVs), which preferentially infect cancer cells and induce host anti-tumor immune responses, have emerged as an effective melanoma therapy. Tanapoxvirus (TANV), which possesses a large genome and causes mild self-limiting disease in humans, is potentially an ideal OV candidate. Interleukin-...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009617666170630143931
更新日期:2018-01-01 00:00:00
abstract::Cetuximab (IMC-C225, Erbitux ImClone Systems Inc, New York, NY) is a recombinant, human/mouse chimeric monoclonal antibody (MAb) that binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR) on both normal and tumor cells, and competitively inhibits the binding of epidermal g...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910790980241
更新日期:2010-02-01 00:00:00
abstract::The epidermal growth factor (EGFR) and its receptor were discovered nearly 40 years ago. Over the past decade interruption of this pathway has been exploited in the treatment of various solid tumors. Antibodies that interfere with ligand binding to and dimerization of the EGFR (and small molecules that inhibit the EGF...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907782418365
更新日期:2007-11-01 00:00:00
abstract::Polyisoprenylated proteins (PPs) methylation by polyisoprenylated protein methyl transferase (PPMTase) is counteracted by polyisoprenylated methylated protein methyl esterase (PMPMEase). This is the only reversible step of the polyisoprenylation pathway as the relative amounts of the acid and ester forms are determine...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791859443
更新日期:2010-09-01 00:00:00
abstract::Prevention is one of the most important and promising strategies to control cancer. Many dietary bioactive compounds, mostly phytochemicals, have been found to decrease the risk of carcinogenesis. Modulating the metabolism and disposition pathways of carcinogens represents one of the major mechanisms by which dietary ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907781386669
更新日期:2007-08-01 00:00:00
abstract::AKT is a central signaling molecule in regulating cell survival, proliferation, tumor growth and angiogenesis. Upstream components of AKT signaling pathway such as PI3K, PTEN, and Ras are commonly mutated in many human cancers. Recently it is found that AKT plays an important role in regulating normal vascularization ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800908783497122
更新日期:2008-02-01 00:00:00