期刊
CANCERS
卷 12, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/cancers12051292
关键词
predictive preventive personalized medicine (PPPM; 3PM); paradigm change; Rho GTPases; structure; function; regulation; signaling pathways; molecular cellular tissue level; impairments; healing; inflammation; tumorigenesis; gynecologic oncology; endometrial cancer; breast cancer; cervical cancer; ovarian cancers; metastatic disease; biomarker-set; patient stratification; in-depth diagnostics; therapy resistance; prognosis
类别
资金
- Scientific Grant Agency (VEGA) of the Ministry of Education, Science, Research and Sport of the Slovak Republic [1/0199/17]
- Slovak Research and Development Agency (SRDA) [APVV-16-0021]
- Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universitat Bonn, Germany
Rho guanosine triphospatases (GTPases) resemble a conserved family of GTP-binding proteins regulating actin cytoskeleton dynamics and several signaling pathways central for the cell. Rho GTPases create a so-called Ras-superfamily of GTPases subdivided into subgroups comprising at least 20 members. Rho GTPases play a key regulatory role in gene expression, cell cycle control and proliferation, epithelial cell polarity, cell migration, survival, and apoptosis, among others. They also have tissue-related functions including angiogenesis being involved in inflammatory and wound healing processes. Contextually, any abnormality in the Rho GTPase function may result in severe consequences at molecular, cellular, and tissue levels. Rho GTPases also play a key role in tumorigenesis and metastatic disease. Corresponding mechanisms include a number of targets such as kinases and scaffold/adaptor-like proteins initiating GTPases-related signaling cascades. The accumulated evidence demonstrates the oncogenic relevance of Rho GTPases for several solid malignancies including breast, liver, bladder, melanoma, testicular, lung, central nervous system (CNS), head and neck, cervical, and ovarian cancers. Furthermore, Rho GTPases play a crucial role in the development of radio- and chemoresistance e.g. under cisplatin-based cancer treatment. This article provides an in-depth overview on the role of Rho GTPases in gynecological cancers, highlights relevant signaling pathways and pathomechanisms, and sheds light on their involvement in tumor progression, metastatic spread, and radio/chemo resistance. In addition, insights into a spectrum of novel biomarkers and innovative approaches based on the paradigm shift from reactive to predictive, preventive, and personalized medicine are provided.
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