Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has antitumor activity in cancer associated with the BRCA1 or BRCA2 mutation. (ClinicalTrials.gov number, NCT00516373.)

There have been major advances in our understanding of the cellular and molecular biology of the human malignancies collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Perspective.

Ovarian cancer is responsible for 4% of deaths from cancer in women. Treatment comprises a combination of surgery and chemotherapy, but patients typically experience disease relapse within 2 years of the initial treatment. Further treatment can extend survival, although relapse eventually occurs again. A better understanding of the mechanisms that underlie this drug resistance should allow treatment to be optimized, so that substantial improvements in the outlook for women with this disease can be achieved.

CYP17 blockade by abiraterone acetate is safe and has significant antitumor activity in CRPC. These data confirm that CRPC commonly remains dependent on ligand-activated AR signaling.

Olaparib has antitumor activity in BRCA1/2 mutation ovarian cancer, which is associated with platinum sensitivity.

Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.

Malignant ascites presents a considerable clinical challenge to the management of ovarian cancer, but also provides a wealth of opportunities for translational research. The accessibility of ascitic fluid and its cellular components make it an excellent source of tumour tissue for the investigation of prognostic and predictive biomarkers, pharmacodynamic markers and for molecular profiling analysis. In this Opinion article, we discuss recent advances in our understanding of its pathophysiology, the development of new methods to characterize its molecular features and how these findings can be used to improve the treatment of malignant ascites, particularly in the context of ovarian cancer.Ascites is the excess accumulation of fluid in the peritoneal cavity. Derived from the Greek word askites, meaning bag-like, it is caused by many pathologies; the most common is hepatic cirrhosis, which accounts for 81% of cases 1 . Others causes include heart failure (3%) and tuberculosis (2%), and a substantial minority (10%) is associated with malignancy (TABLE 1). The composition of ascitic fluid is dependent on the disease with which it is associated (BOX 1).The most common primary site of cancer that is associated with ascites is ovarian, accounting for 38% of malignant ascites occurring in females 2 . Patients with other abdominal epithelial malignancies, including pancreatobiliary and gastric cancer, develop ascites in 21% and 18.3% of cases, respectively 3 . Malignant ascites can also develop secondary to extra-abdominal tumours, such as breast and lung cancer, as well as lymphoma.Correspondence to S.B.K. stan.kaye@rmh.nhs.uk. Competing interests statementThe authors declare no competing financial interests. Europe PMC Funders GroupAuthor Manuscript Nat Rev Cancer. Author manuscript; available in PMC 2015 December 09. Published in final edited form as:Nat Rev Cancer. 2013 April ; 13(4): 273-282. doi:10.1038/nrc3432. Europe PMC Funders Author Manuscripts Europe PMC Funders Author ManuscriptsIn many forms of malignancy, ascites is a sign of advanced disease and poor prognosis 3,4 , with only 11% of patients surviving longer than 6 months 2 . Epithelial ovarian cancer (EOC) is the exception. The majority of women with ovarian cancer present with advanced disease (stage III or stage IV) that may include ascites. In these patients, treatment with surgery together with combination chemotherapy has resulted in a median progression-free survival of 16-22 months and a 5-year survival rate of 27% 5 , although better results are now being reported with improvements in therapy. One study has suggested that ascites at presentation is an independent prognostic factor for time to relapse 6 and, overall, more than one-third of women with ovarian cancer develop ascites during the course of their disease 3 , and this is not limited to any specific histological subtype. Although some oncologists consider that the incidence of ascites may be reducing with the widespread use of combination chemotherapy that incorporates taxanes, th...

ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.