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Review
. 2013 May 2;14(5):9536-55.
doi: 10.3390/ijms14059536.

Targeting signaling pathways in epithelial ovarian cancer

Elisabeth Smolle  1 , Valentin Taucher, Martin Pichler, Edgar Petru, Sigurd Lax, Johannes Haybaeck
Affiliations
Review

Targeting signaling pathways in epithelial ovarian cancer

Elisabeth Smolle et al. Int J Mol Sci. .

Abstract

Ovarian carcinoma (OC) is the most lethal gynecological malignancy. Response to platinum-based chemotherapy is poor in some patients and, thus, current research is focusing on new therapy options. The various histological types of OC are characterized by distinctive molecular genetic alterations that are relevant for ovarian tumorigenesis. The understanding of these molecular pathways is essential for the development of novel therapeutic strategies.

Purpose: We want to give an overview on the molecular genetic changes of the histopathological types of OC and their role as putative therapeutic targets. In Depth Review of Existing Data: In 2012, the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, was approved for OC treatment. Bevacizumab has shown promising results as single agent and in combination with conventional chemotherapy, but its target is not distinctive when analyzed before treatment. At present, mammalian target of rapamycin (mTOR) inhibitors, poly-ADP-ribose polymerase (PARP) inhibitors and components of the EGFR pathway are in the focus of clinical research. Interestingly, some phytochemical substances show good synergistic effects when used in combination with chemotherapy.

Conclusion: Ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative options to bevacizumab available for OC patients. Novel targets which can be assessed before therapy to predict efficacy are needed. The assessment of therapeutic targets is continuously improved by molecular pathological analyses on tumor tissue. A careful selection of patients for personalized treatment will help to reduce putative side effects and toxicity.

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Figures

Figure 1
Figure 1
Type I/low grade (A, C) and type II/high grade (B, D) serous ovarian carcinoma. High grade serous carcinoma is characterized by a significantly higher degree of nuclear atypia and higher number of mitosis compared to low grade serous carcinoma. The papillae are less well preserved in high grade compared to low grade serous carcinomas. HE, 100× (A, B) and 200× (C, D).
Figure 2
Figure 2
Mucinous (A), endometrioid (B), clear cell carcinoma (C) and mixed malignant mesodermal tumor (MMMT) (D). HE, 100×.
Figure 3
Figure 3
Molecular tumorigenesis of type I and type II ovarian carcinoma (modified according to Kurman, Shih 2004, Lax 2009).
See this image and copyright information in PMC

References

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