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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epithelial growth factor receptor (EGFR) appears as a key element in carcinogenesis. It displays high levels of expression in some tumor types. Its activation induces cell proliferation, angiogenesis, cell mobility and inhibition of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules tyrosine kinase inhibitors have been developed. For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats. Immunohistochemistry appears to be the most appropriate test for clinical use, but standardized assays and scoring systems are mandatory. Pathologists are involved in the selection of patients for a monoclonal antibody based targeted treatment, Erbitux, and numerous standardization efforts are provided. No consensus has been reached, to date, for a scoring system. Whether the EGFR status has to be tested for the selection of patients is a non answered question. The selection of the "right patient for the right treatment" might be through the evaluation of other putative markers involved in resistance. EGFR testing may be required before targeted treatment. An exciting endpoint might be the functional and dynamic evaluation of EGFR and downstream proteins, for patients, before and during treatment. The exact role of the pathologist still have to be accurately determined.
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PMID:[The pathologist and EGFR in 2004: I like you, nor do it]. 1573 67

Recently, major developments in the treatment of colon cancer have emerged. These developments include improvements in surgical technique and staging and the introduction of new molecularly targeted pharmacologic agents. Improvements in surgical management involve enhanced staging techniques, allowing more accurate determination of risk of recurrence. Newer agents, such as oxaliplatin, cetuximab, and bevacizumab, now are approved for the treatment of colon cancer. The data associated with use of oxaliplatin in adjuvant and metastatic settings continue to mature; survival benefits are expected to become more fully apparent in the next two years. Bevacizumab, a monoclonal antibody that neutralizes vascular endothelial growth factor, when combined with irinotecan, 5-fluorouracil, and leucovorin (IFL), was superior to IFL alone in achieving median and progression-free survival. Cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor, when given in combination with irinotecan, achieved an increased objective response and increased time to progression, compared with cetuximab alone, in patients refractory to irinotecan-containing regimens. In addition to surgical and pharmacologic developments, the recognition that genetics and molecular markers play an important role in carcinogenesis has heightened research to integrate this knowledge into practice. Nurses play a pivotal role in the care of patients with colon cancer and must be conversant in the new advances in treatment.
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PMID:Therapeutic options in the management of colon cancer: 2005 update. 1575 97

Epithelial growth factor receptor (EGFR) appears as a key element in colorectal carcinogenesis. It displays high levels of expression. Its activation induces cell proliferation, angiogenesis, cell mobility and inhibition of apoptosis. EGFR inhibitors such as monoclonal antibodies or small molecules tyrosine kinase inhibitors have been developed. For EGFR, the diversity of the activation means (amplification, mutation, enhanced transcription, ligands...) leads to technical caveats. Pathologists are involved in the selection of patients for a monoclonal antibody based targeted treatment, Erbitux (cetuximab), and numerous standardization efforts are provided. No consensus has been reached, to date, for a scoring system for immunohistochemistry. No correlation has been found so far between EGFR level of expression and response to cetuximab. Whether and how the EGFR status has to be tested for the selection of patients is a non answered question. The selection of the "right patient for the right treatment" might be through the evaluation of other putative markers involved in resistance. EGFR testing may be required before targeted treatment. An exciting endpoint might be the functional and dynamic evaluation of EGFR and downstream proteins for patients, before and during treatment.
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PMID:[EGFR expression in colorectal cancer and role in tumorigenesis]. 1638 63

Human cancer is caused by multiple factors, such as genetic predisposition, chronic persistent inflammation, environmental factors, life style, and aging. Dysregulated proliferation, dysregulated adhesion, resistance to apoptosis, resistance to senescence, and resistance to anti-cancer drugs are features of cancer cells. Accumulation of multiple epigenetic changes and genetic alterations of cancer-associated genes during multi-stage carcinogenesis results in more malignant phenotypes. Post-genome science is characterized by omics data related to genome, transcriptome, proteome, metabolome, interactome, and epigenome as well as by high-throughput technology, such as whole-genome tiling oligonucleotide array, array CGH with 32,433 overlapping BAC clones, transcriptome microarray, mass spectrometry, tissue-based expression array, and cell-based transfection array. Benchtop oncology supplies Desktop oncology with large amounts of omics data produced by high-throughput technology. Desktop oncology establishes knowledge on cancer-related biomarkers, such as predisposition markers, diagnostic markers, prognostic markers, and therapeutic markers, by using bioinformatics and human intelligence of experts for data mining and text mining. Bedside oncology applies the knowledge established by Desktop oncology to determine therapeutics for cancer patients. Antibody drugs (Trastuzumab/Herceptin, Cetuximab/Erbitux, Bevacizumab/Avastin, et cetera), small molecule inhibitors for tyrosine kinases (Gefitinib/Iressa, Erlotinib/Tarceva, Imatinib/Gleevec, et cetera), conventional cytotoxic drugs, and anti-hormonal drugs are used for cancer chemotherapy. Biomarker monitoring contributes to therapeutic optional choice and drug dosage determination for cancer patients. Knowledge on biomarkers is feedforwarded from desktop to bedside in the translational research, and then biomarker monitoring is feedbacked from bedside to desktop in the reverse translational research. Desktop oncology is indispensable for cancer research in the post-genome era. Combination of genetic screening for cancer predisposition in the general population and precise selection of therapeutic options during cancer management could contribute to the realization of personalized prevention and to dramatically improve the prognosis of cancer patients in the future.
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PMID:Bioinformatics for cancer management in the post-genome era. 1655 Nov 36

The role of epidermal growth factor receptor (EGFR)-driven signaling in different stages of colorectal carcinogenesis, as well in the acquisition of therapy resistance, has been established. Multiple strategies have been developed for the therapeutic targeting of EGFR. Cetuximab is a chimeric monoclonal antibody selective for EGFR with efficacy alone or in combination with irinotecan in the treatment of metastatic colorectal cancer patients, who have progressed to using irinotecan-containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Based on this data, the combination of cetuximab with standard chemotherapy regimens such as irinotecan/ 5-FU/folinic acid (FA) or oxaliplatin/5-FU/FA are currently being investigated in Phase III trials for chemotherapy-naive patients with metastatic colorectal cancer.
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PMID:Cetuximab in the treatment of colorectal cancer. 1655 87

The interest of anti-EGFR therapies has been explored very early in colorectal cancers because of a major contribution of the alterations of the pathway they initiate in colorectal carcinogenesis. Anti-EGFR monoclonal antibodies have shown their potential activity, especially cetuximab (Erbitux((R))) and recently panitumumab. The absence of response predictive factors raises some difficulties in the optimal prescription of this drug. Other anti-EGFR antibodies as well as small molecules inhibiting tyrosine kinase activity are currently explored in gastro-intestinal oncology.
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PMID:[EGF receptors in colorectal cancers]. 1796 93

The epidermal growth factor receptor (EGFR) has been shown to be a promising therapeutic target in head and neck cancer. Cetuximab, a monoclonal antibody against EGFR, has been approved in the United States for use with radiotherapy for head and neck squamous cell carcinoma. However, the role of EGFR targeting agents in other therapeutic modalities, such as combined chemoradiotherapy or induction chemotherapy, remains to be defined. Although results from several clinical trials have demonstrated the therapeutic potentials of EGFR targeting agents in these settings, further studies are necessary before definitive conclusions can be made. The concurrent targeting of EGFR along with other pathways important in carcinogenesis may hold significant therapeutic potential. In particular, several clinical trials are studying the effects of combining agents that target the vascular endothelial growth factor with EGFR inhibitors. Last, studies are ongoing to elucidate the predictive and correlative biomarkers in anti-EGFR therapy to allow for proper patient selection. In the case of cetuximab, these correlative biomarkers may include elements of the immune system in addition to the signal transduction proteins involved in EGFR pathway.
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PMID:Emerging perspectives in epidermal growth factor receptor targeting in head and neck cancer. 1838 30

Colorectal carcinoma (CRC) represents a serious problem worldwide: in the Slovak republic are diagnosed about 2600 new CRC cases annually and its incidence is increasing. Colorectal cancer patients may succumb to the disease because of local recurrence or local formation of metastasis. Therefore, it is necessary to modulate therapeutic algorithm with new methods, leading to early diagnostic of CRC or changing the existing therapeutic procedures. Recent progresses have been made in understanding of EGFR pathway involved in CRC carcinogenesis, especially the role of Ras protein. Mutations in KRAS oncogene are frequently found in human cancers, particularly colorectal, pancreatic, billiary tract and lung tumors. The presence of the KRAS mutations in metastatic colorectal cancer patients correlates with lack of response to the certain epidemal growth factor receptor (EGFR) inhibitor therapies, such as Panitumumab and Cetuximab. Consequently, screening for KRAS mutations status may be used as a prognostic marker, because the CRC patients with KRAS positive tumors have a worse prognosis. The aim of our study was to establish the methods for rapid and sensitive detection of KRAS mutation status in formalin fixed paraffin embedded (FFPE) tissues DNA. We applied Real Time PCR analysis (TheraScreen KRAS Mutation Test Kit) and sequencing analysis (optimised for the analysis of FFPE tissues) to detect somatic mutations in codon 12 and 13 of KRAS gene. Both methods were used concurrently in the panel of DNA isolated from 25 colorectal FFPE tissues tumor. The positive or negative results from all 25 samples were identified by both methods independently. The KRAS mutations were presented in 8 of 25 patients (32%). Our results demonstrate that the Real Time PCR analysis can be used for detection of somatic KRAS mutations in FFPE clinical samples. However, we also recognize that the sequencing analysis of approximately 200bp amplicons may be used for mutations status screening, but with care of method sensitivity.
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PMID:Genetic analysis of KRAS mutation status in metastatic colorectal cancer patients. 1930 32

Targeting the molecular pathways associated with carcinogenesis remains the greatest opportunity to reduce treatment-related morbidity and mortality. Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a cell surface molecule known to promote tumor growth and angiogenesis in preclinical studies of head and neck carcinoma making it an excellent therapeutic target. To evaluate the feasibility of anti-EMMPRIN therapy, an ex-vivo human head and neck cancer model was established using specimens obtained at the time of surgery (n=22). Tumor slices were exposed to varying concentrations of anti-EMMPRIN monoclonal antibody and cetuximab for comparison purposes. Cetuximab is the only monoclonal antibody currently approved for the treatment of head and neck carcinoma. After treatment, tumor slices were assessed by immunohistochemistry and western blot analysis for apoptosis (TUNEL) and EMMPRIN expression. Of the tumor specimens 33% showed a significant reduction in mean ATP levels after treatment with cetuximab compared with untreated controls, whereas 58% of the patients responded to anti-EMMPRIN therapy (P<0.05). Samples, which showed reactivity to anti-EMMPRIN, also had greater EMMPRIN expression based on immunohistochemistry staining (49%) when compared with nonresponders (25%, P=0.06). In addition, TUNEL analysis showed a larger number of cells undergoing apoptosis in antibody-treated tumor slices (77%) compared with controls (30%, P<0.001) with activation of apoptotic proteins, caspase 3 and caspase 8. This study shows the potential of anti-EMMPRIN to inhibit proliferation and promote apoptosis and suggests its future role in the targeted treatment of head and neck carcinoma.
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PMID:Anti-EMMPRIN antibody treatment of head and neck squamous cell carcinoma in an ex-vivo model. 2070 44

More than 90% of all head and neck cancers are squamous cell carcinoma. Despite advances in the management of patients with this disease, the survival rate has not been significantly improved. Several mechanisms of carcinogenesis have been elucidated and molecular targeted agents seem to be promising therapeutic tools. Cetuximab, a monoclonal antibody inhibitor of the EGF receptor, improves survival rates in association with radiotherapy in advanced squamous cell carcinoma of the head and neck (SCCHN) or in palliative disease, and is nowadays the only targeted agent approved in this indication. Other targeted agents are also clinically relevant to the treatment of different malignancies, including SCCHN. This article focuses on the major molecular pathways implicated in SCCHN carcinogenesis and provides an overview of their therapeutic implications.
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PMID:Molecular biology of squamous cell carcinoma of the head and neck: relevance and therapeutic implications. 2083 82


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