BackgroundPancreatic cancer remains one of the most difficult cancers to treat with the poorest prognosis. The key to improving survival rates in this disease is early detection and monitoring of disseminated and residual disease. However, this is hindered due to lack reliable diagnostic and predictive markers which mean that the majority of patients succumb to their condition within a few months.MethodsWe present a pilot study of the detection circulating free DNA (cfDNA) combined with tumor specific mutation detection by digital PCR as a novel minimally invasive biomarker in pancreatic ductal adenocarcinoma (PDAC). This was compared to the detection of CTC by the CellSearch® system and a novel CTC enrichment strategy based on CD45 positive cell depletion. The aim of the study was to assess tumor specific DNA detection in plasma and CTC detection as prognostic markers in PDAC.ResultsWe detected KRAS mutant cfDNA in 26 % of patients of all stages and this correlated strongly with Overall Survival (OS), 60 days (95 % CI: 19–317) for KRAS mutation positive vs 772 days for KRAS mutation negative (95 % CI: 416–1127). Although, the presence of CTC detected by the CellSearch® system did correlate significantly with OS, 88 days (95 % CI: 27–206) CTC positive vs 393 days CTC negative (95 % CI: 284–501), CTC were detected in only 20 % of patients, the majority of which had metastatic disease, whereas KRAS mutant cfDNA was detected in patients with both resectable and advanced disease.ConclusionsTumor specific cfDNA detection and CTC detection are promising markers for the management of patients with PDAC, although there is a need to validate these results in a larger patient cohort and optimize the detection of CTC in PDAC by applying the appropriate markers for their detection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1779-7) contains supplementary material, which is available to authorized users.
Ovarian cancer is the leading cause of death in women with gynecological cancer, since a large proportion of patients are diagnosed at later stages of the disease. The incidence of ovarian cancer in the general population is %, but patients with germline mutations in the BRCA genes have a risk of developing ovarian cancer of up to % with a cumulative risk of ovarian cancer at years of age of % in BRCA and % in BRCA mutation carriers. Although it is a chemosensitive tumor, most of the patients after surgery and chemotherapy based on taxanes and platinum will relapse later in life. Due to the high risk of developing ovarian cancer in patients with BRCA germline mutations, new treatments rely increasingly on histological and molecular characteristics of the primary tumor, achieving greater selectivity and lower toxicity compared with standard cytotoxic agents. Poly ADP-ribose polymerase PARPS inhibitors are the first biologically active agents for patients with ovarian cancer with alterations in the DNA repair pathway, particularly in the high-grade serous subtype of ovarian cancer.The results of clinical trials published so far mean that olaparib has been approved, pending the results of the Phase III trials. The European Medicines Agency EMA adopted olaparib lynparza ® on the December , , as a maintenance therapy after response to platinum-based chemotherapy in relapsed platinum-sensitive ovarian cancer patients with a BRCA mutation. By contrast, the Food and Drug Administration FDA approved olaparib on December , , in patients with high-grade ovarian epithelial serous tumors and a BRCA mutation who have progressed during three or more lines of chemotherapy. Olaparib is also used in primary fallopian tube and peritoneal cancers with BRCA mutations.
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