**Author details**

risk over time [264] while heavy smoking (>10 packs per day) more than doubles the risk of developing ovarian cancer [265]. Alcohol consumption increased the risk of ovarian cancer, but seems to have an effect only in heavy drinkers. Consumption of more than 20 drinks per week is associated with increased risk [266] while with moderate use the risk is less pronounced or significant [267, 268]. Obesity is associated with less common subtypes of ovarian cancer and not HGS [269] and the lifetime risk decreases with recreation physical activity [270]. Finally, inflammation increases the risk of developing ovarian cancer [271] while the use of aspirin was shown to reduce risk of developing ovarian cancer from between 20 and 34% [272]. The use of other non-steroidal anti-inflammatory drugs (NSAIDs) showed a reduc-

Genetically, ovarian cancer is a heterogeneous and dynamic disease that presents several clinical and research challenges. While epithelial ovarian cancer is categorized pathologically into five basic subtypes, within each subtype exist genetic diversity that limits the development of target therapies. To add to this complexity, one of the hallmarks of serous ovarian cancer is genomic instability, which is driven by frequent *TP53* mutations and deficiencies in DNA repair pathways. While this genomic alterations have led to the development of breakthrough therapies (PARP inhibitors), they also contributes to the dynamic cell growth and frequent genomic alterations and gene expression changes which contribute to the adaptation to therapy. Likewise, the pathogenesis of ovarian cancer remains a debated field with the recent insights of progression of a subset of serous ovarian cancer from fallopian tube epithelial lesions. Progression from the fallopian tube means tumors detected on the ovarian surface are already metastatic disease, leading to quick progression and limited response to therapy. Overall, while many genetic and genomic abnormalities have been identified in ovarian cancer, additional discovers are needed to (1) improve early detection of the disease (at a time when current treatment might be curative), (2) further define molecular classifiers of response to therapy, and (3) develop therapies that will be more effective across or specific to the different molecular subtypes. Other than the very common *TP53* mutation in high-grade serous ovarian cancer (96% of cases), which to date is undruggable, and the previously mentioned *BRCA* mutations (approximately 10–12% of ovarian cancers), only a small overall percentage of tumors from patients with this malignancy will be found to possess a specific causative mutation that can be effectively targeted therapeutically. Therefore, implementation of genomicbased medicine remains a challenge for the management of women with ovarian cancer.

Pathology images for each ovarian cancer subtype generously provided by Dr. Rashna Madan from the University of Kansas Medical Center and the University of Kansas Cancer Center

tion in risk but was not significant.

20 Ovarian Cancer - From Pathogenesis to Treatment

**5. Conclusion**

**Acknowledgements**

(Kansas City, KS).

Jeff Hirst<sup>1</sup> \*, Jennifer Crow1 and Andrew Godwin1,2

\*Address all correspondence to: jhirst@kumc.edu

1 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA

2 University of Kansas Cancer Center, University of Kansas Medical Center, Kansas City, KS, USA
