Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Abstract

IntroductionIn developed countries, ovarian cancer is the fourth most common cancer in women. Due to the non-specific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets.MethodsWe have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription.Results and conclusionAnalysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies.

A Comparative Analysis of Genetic and Epigenetic Events of Breast and Ovarian Cancer Related to Tumorigenesis

“…As chemotherapy of ovarian cancer is mainly target non-specific, and because epigenetic modifications possibly play similar types of roles in ovarian and breast cancers, current investigators are extremely encouraged to develop epigenetic therapies in combination with traditional drugs for breast and ovarian cancers. [ 50 , 61 , 62 , 91 , 92 , 94 , 96 , 97 , 98 , 99 ].…”

Epigenetics in ovarian cancer

“…HDACs, which are aberrantly expressed in a number of cancers including ovarian cancer [47], are comprised of eighteen proteins grouped into four classes; classes I, II and IV HDACs are zinc dependent enzymes, while class III are NAD+ dependent [48]. Class III HDACs include the sirtuin enzymes, products of the SIRT1 - SIRT7 gene family [49].…”

Epigenetics in ovarian cancer: premise, properties, and perspectives

“…Malignant ovarian tumor has the highest mortality rate among all gynecological cancers [ 1 ]. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer [ 2 ]. In general, the majority of EOC patients are diagnosed in advanced stage (Stage III or IV) disease, due to the non-specific symptoms characteristic of early stage EOC and the lack of available EOC-specific screening biomarkers.…”