Poly(ADP-ribose) polymerases have shown true promise in early clinical studies due to reported activity in BRCA-associated cancers. PARP inhibitors may represent a potentially important new class of chemotherapeutic agents directed at targeting cancers with defective DNA-damage repair. In order to widen the prospective patient population that would benefit from PARP inhibitors, predictive biomarkers based on a clear understanding of the mechanism of action are required. In addition, a more sophisticated understanding of the toxicity profile is required if PARP inhibitors are to be employed in the curative, rather than the palliative, setting. PARP inhibitors have successfully moved into clinical practice in the past few years, with approval granted from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) within the past two years. The United States FDA approval of olaparib applies to fourth-line treatment in germline BRCA-mutant ovarian cancer, and European EMA approval of olaparib for maintenance therapy in both germline and somatic BRCA-mutant platinum-sensitive ovarian cancer. This review covers the current understanding of PARP, its inhibition, and the basis of the excitement surrounding these new agents. It also evaluates future approaches and directions required to achieve full understanding of the intricate interplay of these agents at the cellular level.

Objectives. Defining precisely the normal range of HE4 protein is crucial for the proper interpretation of tumor marker results and for a more efficient diagnosis of ovarian malignancy. The aim of our study was to evaluate a reference limit of HE4 protein in a population to promote and facilitate the common use of HE4 protein assays. We also tried to identify potential association of HE4 levels with other conditions such as smoking, age, BMI, and creatinine levels. Methods. Blood samples were collected from 617 patients divided into three groups: healthy, pregnant, and with benign ovarian tumors. Serum HE4 concentrations were measured following a standard procedure. HE4 reference ranges for each group and association of HE4 levels with BMI, creatinine, and smoking were investigated. Results. HE4 reference limit for healthy patients equals 85 pmol/l, which becomes 73 pmol/l and 93 pmol/l for pre and postmenopausal subgroups, respectively. There is a statistically significant correlation between HE4 serum level and smoking (p=0.000001) and there is no correlation with creatinine. But if we take into account age and smoking, in multivariate analysis, there is a correlation. For pregnant, the upper limit values of normal HE4 levels are 55 pmol/l (median=40 pmol/l), 80 pmol/l (median=43 pmol/l), and 106 pmol/l (median=53 pmol/l) for the first, second, and third trimesters, respectively. Conclusions. HE4 protein value strongly depends on the patient’s age and smoking. The serum concentration of HE4 marker increases with the duration of pregnancy. Understanding the normal range of HE4 protein enables the correct interpretation of marker measurements. This may result in an earlier and more effective diagnosis of ovarian cancer.

HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic and paraaortic lymphadenectomy.

BackgroundMetastasis is a common feature of many advanced stage cancers and metastatic spread is thought to be responsible for cancer progression. Most cancer cells are localized in the primary tumor and only a small population of circulating tumor cells (CTC) has metastatic potential. CTC amount reflects the aggressiveness of tumors, therefore their detection can be used to determine the prognosis and treatment of cancer patients.The aim of this study was to evaluate human chorionic gonadotropin beta subunit (CGB) and gonadoliberin type 1 (GNRH1) expression as markers of tumor cells circulating in peripheral blood of gynecological cancer patients, indicating the metastatic spread of tumor.MethodsCGB and GNRH1 expression level in tumor tissue and blood of cancer patients was assessed by real-time RT-PCR. The data was analyzed using the Mann-Whitney U and Spearman tests. In order to distinguish populations with homogeneous genes' expression the maximal likelihood method for one- and multiplied normal distribution was used.ResultReal time RT-PCR results revealed CGB and GNRH1 genes activity in both tumor tissue and blood of gynecological cancers patients. While the expression of both genes characterized all examined tumor tissues, in case of blood analysis, the transcripts of GNRH1 were found in all cancer patients while CGB were present in 93% of patients. CGB and GNRH1 activity was detected also in control group, which consisted of tissue lacking cancerous changes and blood of healthy volunteers. The log-transformation of raw data fitted to multiplied normal distribution model showed that CGB and GNRH1 expression is heterogeneous and more than one population can be distinguished within defined groups.Based on CGB gene activity a critical value indicating the presence of cancer cells in studied blood was distinguished. In case of GNRH1 this value was not established since the results of the gene expression in blood of cancer patients and healthy volunteers were overlapping. However one subpopulation consists of cancer patient with much higher GNRH1 expression than in control group was found.ConclusionsAssessment of CGB and GNRH1 expression level in cancer patients' blood may be useful for indicating metastatic spread of tumor cells.

Objectives: The aim of this study was to assess the sensitivity and specificity of HE4 in detecting and differentiating between types I and II epithelial ovarian cancer (EOC)