Abstract
Despite advances in surgical and chemotherapeutic treatment options, less than 50% of patients with advanced-stage ovarian cancer survive five years after initial diagnosis. In this regard, novel treatment approaches are warranted utilizing molecularly targeted therapies directed against particular components of specific signaling pathways which are required for tumor development and progression. One molecular pathway of interest is the hedgehog (Hh) signaling pathway. Activation of the Hh pathway has been observed in several cancer types, including ovarian cancer. This review highlights the crucial role of Hh signaling in the development and progression of ovarian cancer and might lead to a better understanding of the Hh signaling in ovarian tumorigenesis, thus encouraging the investigation of novel targeted therapies.
Highlights
Ovarian cancer is the fifth most lethal gynecologic malignancy in the Western world with an estimated 22,280 new cases and 15,500 deaths in 2012 in the United States alone [1]
The role of PTCH1 has been further demonstrated in knockout mice: mice heterozygous for PTCH1 null mutation showed essential features observed in patients with Gorlin syndrome, such as malignant tumors and developmental defects, such as spina bifida occulta [45,46,53]
In Barrett’s esophagus, an early precursor of esophageal adenocarcinomas, the expression of Sonic hedgehog (Shh) and Ihh is increased in the epithelium, which is associated with stromal expression of the Hh target genes PTCH1 and BMP4 [59]
Summary
Ovarian cancer is the fifth most lethal gynecologic malignancy in the Western world with an estimated 22,280 new cases and 15,500 deaths in 2012 in the United States alone [1]. The major unresolved clinical problems associated with ovarian cancer include malignant progression and rapid emergence of drug resistance against conventionally used chemotherapeutic agents. The Hh pathway is involved in regulating differentiation and proliferation, including cell fate and number, in brains and spinal cords, and the pattern of limbs and internal organs, so that developing tissue reaches its correct size with the appropriate cell types and adequate degrees of vascularization and innervation. Hh signaling promotes proliferation, regeneration and differentiation of somatic tissues in adults [6] It plays a pivotal role for maintaining the tissue stem cell population [10]. We give an overview regarding the signal transduction of the Hh pathway and discuss the role of Hh signaling in development and progression of cancer with special emphasis on ovarian cancer and its potential impact on future therapeutic strategies
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