TY - JOUR
T1 - The IGF hormonal network in endometrial cancer
T2 - Functions, regulation, and targeting approaches
AU - Bruchim, Ilan
AU - Sarfstein, Rive
AU - Werner, Haim
PY - 2014
Y1 - 2014
N2 - Epidemiological as well as clinical and experimental data identified the insulin-like growth factors (IGF1, IGF2) as important players in gynecological cancers in general, and endometrial tumors in particular. The IGF1 receptor (IGF1R), which mediates the proliferative and anti-apoptotic activities of both ligands, emerged in recent years as a promising therapeutic target in oncology. However, most clinical trials conducted so far led to mixed results, emphasizing the need to identify biomarkers that can predict responsiveness to anti-IGF1R-targeted therapies. This article will review recent data regarding the role and expression of IGF system components in endometrial cancer. In addition, we will review data on the interplay between the IGF signaling pathway and tumor suppressors p53 and breast cancer susceptibility gene-1 (BRCA1). Anti-oncogenes p53 and BRCA1 play a key role in the etiology of gynecological cancers and, therefore, their interaction with IGF1R is of high relevance in translational terms. A better understanding of the complex mechanisms underlying the regulation of the IGF system will improve our ability to develop effective treatment modalities for endometrial tumors.
AB - Epidemiological as well as clinical and experimental data identified the insulin-like growth factors (IGF1, IGF2) as important players in gynecological cancers in general, and endometrial tumors in particular. The IGF1 receptor (IGF1R), which mediates the proliferative and anti-apoptotic activities of both ligands, emerged in recent years as a promising therapeutic target in oncology. However, most clinical trials conducted so far led to mixed results, emphasizing the need to identify biomarkers that can predict responsiveness to anti-IGF1R-targeted therapies. This article will review recent data regarding the role and expression of IGF system components in endometrial cancer. In addition, we will review data on the interplay between the IGF signaling pathway and tumor suppressors p53 and breast cancer susceptibility gene-1 (BRCA1). Anti-oncogenes p53 and BRCA1 play a key role in the etiology of gynecological cancers and, therefore, their interaction with IGF1R is of high relevance in translational terms. A better understanding of the complex mechanisms underlying the regulation of the IGF system will improve our ability to develop effective treatment modalities for endometrial tumors.
KW - BRCA1
KW - Biomarkers
KW - Endometrial cancer
KW - IGF1
KW - IGF1 receptor
KW - Insulin-like growth factors
KW - P53
KW - Uterine serous carcinoma
UR - http://www.scopus.com/inward/record.url?scp=84905493633&partnerID=8YFLogxK
U2 - 10.3389/fendo.2014.00076
DO - 10.3389/fendo.2014.00076
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AN - SCOPUS:84905493633
SN - 1664-2392
VL - 5
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
IS - MAY
M1 - 76
ER -