Targeted Therapies in Gynecologic Cancers

Abstract

With the rapid development of high-throughput techniques for identifying novel specific molecular targets in human cancer over the past few years, attention to targeted cancer therapy has dramatically increased. The term "targeted cancer therapy" refers to a new generation of drugs designed to interfere with a specific molecular target that is believed to play a critical role in tumor growth or progression, is not expressed significantly in normal cells, and is correlated with clinical outcome. There has been a rapid increase in the identification of targets that have potential therapeutic application. The clinical success of the small-molecule kinase inhibitor imatinib mesylate in chronic myeloid leukemia and gastrointestinal stromal tumors has accelerated the development of a new era of molecular targeted cancer therapy. The number of agents under preclinical and clinical investigation has grown accordingly. This emphasis on molecular biology and genetics has also resulted in significant changes in the treatment of gynecologic cancers. Several promising drugs targeting tyrosine kinases (EGFR and Her-2/Neu), mTOR, Raf kinase, proteasome, and histone deacetylases, as well as drugs affecting apoptosis and mitosis, are under development for clinical application. However, some clinical trials of p53 gene therapies and farnesyl transferase inhibitors have had limited success. In this review, we will focus on potential novel targets in gynecologic cancer and the development of targeted therapy and its clinical applications in gynecologic cancer.

Inhibition of the Rho/ROCK pathway enhances the efficacy of cisplatin through the blockage of hypoxia-inducible factor-1α in human ovarian cancer cells

“…Several studies have shown the effect of molecular targeting therapies on ovarian cancers. 5 The most promising molecular targeting therapy is the blockade of angiogenesis using antiangiogenic drugs, such as bevacizumab, which is an antibody to vascular endothelial growth factor (VEGF), and a phase III study combining bevacizumab with first-line chemotherapy is currently ongoing to assess its benefits in ovarian cancer patients.…”

Expression profiling of 22 genes involved in the PI3K–AKT pathway identifies two subgroups of high-grade endometrial carcinomas with different molecular alterations

“…In fact, there are actually inhibitors of PI3K and mTOR that may be used as potential anticancer agents. 41 In summary, hierarchical clustering analysis of genes involved in the PI3K-AKT pathway revealed two subgroups of high-grade endometrial carcinomas …”

Trastuzumab therapy vs tetracycline controlled ERBB2 downregulation: influence on tumour development in an ERBB2-dependent mouse tumour model

“…In recent years many scientists have concentrated on the question why some patients respond to trastuzumab whereas others do not (Cappuzzo et al, 2006;Chon et al, 2006;Menendez et al, 2006;Tseng et al, 2006). A correlation between the extent of ERBB2 expression determined by immunohistochemistry or FISH and the clinical response has been observed in several studies (Vogel et al, 2002;Mass et al, 2005;Tsuda, 2006).…”