Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Palliative chemotherapy for metastatic colorectal cancer has undergone substantial changes in recent years. The implementation of modern biologicals in the treatment has substantially improved overall survival up to 30 months. With the increasing number of therapeutic options, the question of optimal treatment sequence arises, which is addressed in current studies like FIRE 4 or STRATEGIC-1. Furthermore, clinical and molecular biomarkers to predict efficacy and tolerability are urgently needed. Today, the detection of activating RAS mutations is the only validated biomarker which precludes patients from anti-EGFR treatment. The detection of BRAF mutation V600E is associated with a very poor prognosis corresponding to a survival of 9-12 months. Prospective trials evaluating an optimal approach to this subgroup are still missing. First results from strategies targeting the aberrant signal transduction are promising and require further validation. Despite the advances so far, life expectancy unfortunately continues to be limited in the majority of patients with metastatic colorectal cancer. New strategies are needed to improve the prognosis. To this end, the identification of Her2/neu as a potential target and first experiences with checkpoint inhibition in patients with mismatch repair-deficient tumors are promising and also require further validation.
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PMID:Treatment of Metastatic Colorectal Cancer: Standard of Care and Future Perspectives. 2749 45

Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands' neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low: 192 vs. high: 16), HER2/neu (low: 201 vs. high: 7) and HER3 (low: 69 vs. high: 139) expressions were assessed in 208 patients. High versus low NRG1 expression significantly affected progression-free survival (PFS) [4.7 vs. 8.2 months, hazard ratio (HR): 2.45; 95% confidence interval (CI): 1.45-4.13; P=0.001], but not overall survival (OS) (15.5 vs. 20.7 months, HR: 1.33; 95% CI: 0.76-2.35; P=0.32). High versus low HER3 expression (PFS: 7.1 vs. 8.8 months, HR: 1.11; 95% CI: 0.82-1.50; P=0.50; OS: 19.8 vs. 21.1 months, HR: 0.95; 95% CI: 0.70-1.30; P=0.75) and high compared with low HER2/neu expression (PFS: 7.7 vs. 8.0 months, HR: 1.07; 95% CI: 0.71-1.60; P=0.75; OS: 16.6 vs. 21.1 months, HR: 1.13; 95% CI: 0.75-1.71; P=0.57) did not influence outcome. High NRG1 expression was associated with inferior PFS in the FIRE-1 trial. We did not detect a prognostic impact of HER2/neu and HER3 overexpression in mCRC. The frequency of overexpression was comparable with other studies.
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PMID:Prevalence and influence on outcome of HER2/neu, HER3 and NRG1 expression in patients with metastatic colorectal cancer. 2858 79