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)

A principal difference between malignant and normal cells is the aberrant expression of oncogenes. Previously, we have reported on the expression of the insulin-like growth factor 1 receptor (IGF-1-R) in 93% of the human primary breast cancers studied. In the present study, we observed an increased gene copy number of the IGF-1-R in only 19 (2%) of 975 cases studied. The gene copy number of tumors with an amplified IGF-1-R gene varies between 3 and 56 (median, 24 copies). In 11 breast tumor samples with high (greater than or equal to 20 copies) IGF-1-R gene copy numbers, an additional amplification of either the c-myc gene (n = 3) or int-2/bcl-1 genes (n = 5) was observed, whereas no amplification of the HER2/neu gene was detected. The c-fes gene (like the IGF-1-R gene located on chromosome 15q25-qter), was found coamplified with the IGF-1-R in two cases, in one case to the same high extent (38 gene copies, each) and in the other case to only a moderate extent (4 copies of the c-fes gene and 21 copies of the IGF-1-R gene). Tumors with an amplified IGF-1-R gene showed a noticeable increased expression of the IGF-1-R as measured by ligand binding assays on membrane preparations. The median amount of the IGF-1-R protein of the amplified tumors was observed to be 35 times higher when compared to nonamplified tumors (P less than 0.001). Patients with tumors containing a high (greater than or equal to 20 copies) IGF-1-R gene copy number tend to have a shorter median overall survival (42 months; range, 14-120+; n = 8) than patients with tumors having a low amplified (3-10 copies) IGF-1-R gene copy number (median, 77 months; range, 19.5-98+; n = 4).
 ...
PMID:Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. 131 Jun 36

Urothelial carcinoma (UC) is a common and deadly cancer in the United States. While molecularly targeted therapies have been integrated into the standard-of-care management of other solid tumors in recent years, the use of targeted therapy in UC has lagged behind. Accordingly, the management of advanced disease, along with outcomes, has remained largely unchanged for the past 2 decades. Despite the lack of new agents in the clinic, preclinical and early clinical studies have demonstrated that numerous potentially"targetable" molecular pathways exist, including the epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), human epidermal growth factor receptor 2 (HER2/neu), and insulin-like growth factor 1 receptor (IGF1R) pathways. This review focuses on targeted therapies related to these pathways of interest for the treatment of advanced UC, describing the evidence to support further investigation of these approaches. Notably, the identification and validation of new agents will only occur through accrual to urothelial cancer trials designed to answer these questions, which will require the support of the entire urologic community.
 ...
PMID:Targeted therapy in advanced urothelial carcinoma. 2368 95