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 growth factor (EGF) as well as other ligands. Cetuximab binding to the EGFR blocks phosphorylation and activation of receptor-associated kinases and their associated downstream signalling (MAPK, PI3K/Akt, Jak/Stat pathways) resulting in inhibition of many cellular processes such as induction of apoptosis, cell growth, decreased Matrix Metallo-Proteinase (MMPs) and vascular endothelial growth factor (VEGF) production. Cetuximab is also able to display cytotoxic effect through antibody-dependent cellular cytotoxicity (ADCC). In vitro and in vivo experiments elucidated a wide range of biological properties attributed to cetuximab, these include: direct inhibition of EGFR tyrosine kinase activity, inhibition of cell cycle progression, inhibition of angiogenesis, invasion and metastatization processes, activation of pro-apoptotic molecules and synergic cytotoxicity effect with chemotherapy and radiotherapy. Several studies have shown cetuximab is able to inhibit growth of EGFR-expressing tumor cells in vitro as well as in nude mice bearing xenografts of human cancer cell lines. Moreover, numerous clinical trials demonstrated cetuximab efficacy in different tumor types and it is approved by Food and Drugs Administration (FDA) for use in the treatment of metastatic colorectal cancer (mCRC) as single agent or in combination with chemotherapy, for locally/regionally advanced head and neck squamous cell carcinoma (HNSCC) in combination with radiotherapy, and as monotherapy for recurrent/metastatic HNSCC after failing platinum-based chemotherapy. This review will illustrate pre-clinical and clinical data on biological properties of cetuximab focusing on the predictive markers of clinical response to this drug.
journal_name
Curr Cancer Drug Targetsjournal_title
Current cancer drug targetsauthors
Vincenzi B,Zoccoli A,Pantano F,Venditti O,Galluzzo Sdoi
10.2174/156800910790980241subject
Has Abstractpub_date
2010-02-01 00:00:00pages
80-95issue
1eissn
1568-0096issn
1873-5576pii
EPub-Abstract-CCDT-12journal_volume
10pub_type
杂志文章,评审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::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::Oncolytic viruses can selectively replicate in and lead to tumor cell lysis with minimal infection/replication potential in adjoining non-neoplastic tissue. Because of paramount safety concerns, first-generation oncolytic viruses were designed to be significantly attenuated in their lytic potential. Results from recen...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907780058880
更新日期:2007-03-01 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 histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo by inducing cell cycle arrest, differentiation and/or apoptosis. Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regula...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009043481560
更新日期:2004-03-01 00:00:00
abstract::Nuclear Hormone Receptors (NR) represent one of the most promising protein families in terms of therapeutic applications. These transcription factors are naturally switched on and off by small molecule hormones presenting physico-chemical properties very similar to therapeutic chemical entities. NRs represent therefor...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023333845
更新日期:2002-09-01 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::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::The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patient...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170206105131
更新日期:2018-01-01 00:00:00
abstract::Prostate cancer (CaP) is a major health problem in males in Western countries. Current therapeutic approaches are limited and many patients die of secondary disease (metastases). There is no cure for metastatic castration-resistant prostate cancer (CRPC). Targeting tumor-associated antigens is fast emerging as an area...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910791190193
更新日期:2010-05-01 00:00:00
abstract::Anti-angiogenesis therapy is one major approach of cancer therapies nowadays. Unfortunately, anti-angiogenesis therapy targeting VEGF-A was recently stumbled by the drugresistance that results from adaptive mechanisms, such as intratumor hypoxia. To obtain a more efficient therapeutic response, we created and identifi...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800961603160206125352
更新日期:2016-01-01 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::Autophagy is an intracellular lysosomal/vacuolar degradation system, in which the inner cytoplasmic cell membrane is degraded by the lysosomal hydrolases, followed by the resulting products released back into the cytosol. It is involved in many physiological processes which are crucial for cell growth and survival. Ho...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009617666170330124819
更新日期:2018-01-01 00:00:00
abstract::Scaffold-based analogs of cinnamic acid benzyl amide (CABA) exhibit pleiotropic effects in cancer cells, and their exact molecular mechanism of action is under investigation. The present study is part of our systemic analysis of interactions of CABA analogs with their molecular targets. These compounds were shown to i...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009614666140821122718
更新日期:2014-01-01 00:00:00
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::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::MicroRNA-153 (miR-153) is considered to be a tumor regulator. Silencing of miR-153 expression induced apoptosis in breast cancer cells. Data on mechanism suggest that up-regulation of miR- 153 level promotes cell proliferation via the down regulation of the expression of PTEN or FOXO1, which attenuates the proliferati...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/1568009615666150225122635
更新日期:2015-01-01 00:00:00
abstract::Malignant brain tumors including primary brain tumors (e.g., glioblastoma multiforme) and metastases, are aggressive and lethal entities for the majority of affected patients. Current standard treatments involving combinations of surgery, radiotherapy and systemic chemotherapy offer only modest improvements in surviva...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009615666150616123548
更新日期:2015-01-01 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::The capacity to induce new blood vessel formation or to repair damaged vessels is an attractive idea that has, for a long time, captured the attention and imagination of researchers. Beside the identification of the pro-angiogenic growth factors and their counterpart inhibitors, the discovery of endothelial progenitor...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800910793358041
更新日期:2010-12-01 00:00:00
abstract::Ovarian cancer is a leading cause of death worldwide from gynecological malignancies, mainly because there are few early symptoms and the disease is generally diagnosed at an advanced stage. In addition, despite the effectiveness of cytoreductive surgery for ovarian cancer and the high response rates to chemotherapy, ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009618666181010091246
更新日期:2019-01-01 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::Wild-type Wilms' tumor gene WT1 is expressed at high levels not only in most of acute myelocytic, acute lymphocytic, and chronic myelocytic leukemia, but also in various types of solid tumors including lung cancer. We tested the ability of the gene product (WT1) to serve as a target antigen for tumor specific immunot...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009023334088
更新日期:2002-03-01 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::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::The greatest risk factor for the development of cervical and other cancers that have been linked to the human papillomavirus (HPV) family is the persistence of the virus. To persist for the decades required to develop HPV-related cancers, the virus must escape host immunity. HPV is a simple DNA virus that has evolved ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800907780006869
更新日期:2007-02-01 00:00:00
abstract::Anchorage-independent growth, anoikis resistance, and most steps of metastasis formation are integrin-mediated or -dependent processes, which are characteristics of malignant tumor cells. Acting as oncogenes or tumor suppressor genes, integrins may be involved in the oncogenic transformation of normal cells and their ...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/156800906776056518
更新日期:2006-03-01 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::Membrane ion channels participate in cancerous processes such as proliferation, migration and invasion, which contribute to metastasis. Increasing evidence indicates that voltage-dependent K(+) (Kv) channels are involved in the proliferation of many types of cells, including tumor cells. Kv channels have generated imm...
journal_title:Current cancer drug targets
pub_type: 杂志文章
doi:10.2174/156800909790192400
更新日期:2009-12-01 00:00:00
abstract::The ubiquitin system controls protein stability and function. F-box proteins form SCF (SKP1-Cullin1-F-box protein)-type ubiquitin (E3) ligases to selectively target their substrates for degradation via the ubiquitin-proteasome pathway. Here, we review F-box proteins associated with cancer development. S-phase kinase-a...
journal_title:Current cancer drug targets
pub_type: 杂志文章,评审
doi:10.2174/1568009616666151112122231
更新日期:2016-01-01 00:00:00