Current and Futuristic Roadmap of Ovarian Cancer Management: An Overview.

Ovarian cancer (OC) is the most lethal gynecological malignancy among women worldwide. In most cases, it is diagnosed late at an advanced stage and does not respond well to existing therapies leading to its poor prognosis. In addition, other factors including epidemiological, complex histological diversity, multiple molecular alterations, and overlapping signaling pathways are also important contributors to poor disease outcome. Efforts have continued to develop a deeper understanding of the molecular pathogenesis and altered signaling nodes that provide hope for better clinical management through the development of novel approaches for early diagnosis, disease subtyping, prognosis, and therapy. In this chapter, we provide a detailed overview of OC and its histological subtypes and discuss prevalent molecular aberrations and active signaling pathways that drive OC progression. We also summarize various diagnostic and prognostic markers and therapeutic approaches currently being employed and discuss emerging findings that hold the potential to change the future course of OC management.

Clinicopathologic significance and race-specific prognostic association of MYB overexpression in ovarian cancer.

Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.

Racial health disparities in ovarian cancer: not just black and white.

Ovarian cancer (OC) is the most lethal gynecological malignancy, which disproportionately affects African American (AA) women. Lack of awareness and socioeconomic factors are considered important players in OC racial health disparity, while at the same time, some recent studies have brought focus on the genetic basis of disparity as well. Differential polymorphisms, mutations and expressions of genes have been reported in OC patients of diverse racial and ethnic backgrounds. Combined, it appears that neither genetic nor the socioeconomic factors alone might explain the observed racially disparate health outcomes among OC patients. Rather, a more logical explanation would be the one that takes into consideration the combination and/or the interplay of these factors, perhaps even including some environmental ones. Hence, in this article, we attempt to review the available information on OC racial health disparity, and provide an overview of socioeconomic, environmental and genetic factors, as well as the epigenetic changes that can act as a liaison between the three. A better understanding of these underlying causes will help further research on effective cancer management among diverse patient population and ultimately narrow health disparity gaps.

MicroRNAs in gynecological cancers: Small molecules with big implications.

Gynecological cancers (GCs) are often diagnosed at advanced stages, limiting the efficacy of available therapeutic options. Thus, there remains an urgent and unmet need for innovative research for the efficient clinical management of GC patients. Research over past several years has revealed the enormous promise of miRNAs. These small non-coding RNAs can aid in the diagnosis, prognosis and therapy of all major GCs, viz., ovarian cancers, cervical cancers and endometrial cancers. Mechanistic details of the miRNAs-mediated regulation of multiple biological functions are under constant investigation, and a number of miRNAs are now believed to influence growth, proliferation, invasion, metastasis, chemoresistance and the relapse of different GCs. Modulation of tumor microenvironment by miRNAs can possibly explain some of their reported biological effects. miRNA signatures have been proposed as biomarkers for the early detection of GCs, even the various subtypes of individual GCs. miRNA signatures are also being pursued as predictors of response to therapies. This review catalogs the knowledge gained from collective studies, so as to assess the progress made so far. It is time to ponder over the knowledge gained, so that more meaningful pre-clinical and translational studies can be designed to better realize the potential that miRNAs have to offer.