Comprehensive Profiling of EGFR/HER Receptors for Personalized Treatment of Gynecologic Cancers
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REVIEW ARTICLE
Comprehensive Profiling of EGFR/HER Receptors for Personalized Treatment of Gynecologic Cancers Henry D. Reyes • Kristina W. Thiel • Matthew J. Carlson Xiangbing Meng • Shujie Yang • Jean-Marie Stephan • Kimberly K. Leslie
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Ó Springer International Publishing Switzerland 2014
Abstract The primary gynecologic cancers include cancers of the endometrium, ovary, and cervix. Worldwide, cervical cancer is the most common gynecologic cancer, whereas endometrial cancer is the most common in the US. Ovarian cancer is the fifth most deadly cancer in women, with 5-year survival rates for advanced disease at only 27 %. As such, there is an urgent need for reliable screening tools and novel targeted therapeutic regimens for these malignancies. The epidermal growth factor receptor (EGFR)/human EGFR (HER) family of receptors has been associated with the development and progression of many solid tumors. Despite clear roles for these receptors in other cancers, the expression of HER family members in gynecologic cancers and their relationship with disease stage, grade, and response to treatment remain controversial. In
H. D. Reyes K. W. Thiel M. J. Carlson X. Meng S. Yang J.-M. Stephan K. K. Leslie Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA 52242, USA e-mail: [email protected] K. W. Thiel e-mail: [email protected] M. J. Carlson e-mail: [email protected] X. Meng e-mail: [email protected] S. Yang e-mail: [email protected] J.-M. Stephan e-mail: [email protected] X. Meng K. K. Leslie (&) Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242, USA e-mail: [email protected]
this review, we describe the existing evidence for the use of HER family members as diagnostic and prognostic indicators as well as their potential as therapeutic targets in gynecologic cancers.
1 Introduction The human epidermal growth factor receptor (HER) family members are being explored in the clinic as diagnostic tools as well as therapeutic targets for a variety of solid tumors. Originally named for their homology to the erythroblastoma viral gene product, v-erbB, the HER family members have been studied for more than 40 years. In the mid-1990s, HER family members epidermal growth factor receptor (EGFR)/HER1/ErbB1, HER2/ErbB2/neu, HER3/ ErbB3, and HER4/ErbB4 and their ligands were established to play crucial roles in epithelial cell development since HER receptor knockout mice die at early stages of development. HER family members have also been shown to contribute to cancer development and progression, and multiple anticancer therapeutics targeting these receptors have been identified. A comprehensive search of all original research and reviews published in MEDLINE and ClinicalTrials.gov through October 2013 was undertaken using the following key terms: epidermal growth factor receptor; EGFR; HER2; HER3; HER4; endometrial cancer; ovarian cancer; and cervical cancer. Over 200 papers were evaluated, of which 119 are cited in
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