To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently under development for clinical use.

Background Study undertaken to find any association of metformin intake to that of survival in ovarian cancer. Methods In this retrospective case control study, ovarian cancer patients who took metformin (cases) were compared with patients having ovarian cancer but no metformin (controls). Two-layered analysis was conducted. In preliminary analysis, all cases (OC cohort) were compared with controls in 1:2 ratio. Subsequently in definitive analysis, only Epithelial Ovarian Cancer cases (EOC cohort) were compared with controls in 1:3 ratio. In EOC cohort, cases were matched with controls for age (+/−5 years), FIGO stage and residual disease. Prognostic variables and Disease Specific Survival (DSS) were compared with Chi square, Kaplan-Meier (log rank) and Cox proportional hazards. Results In the preliminary analysis on the OC cohort (72 cases, 143 controls), cases had a better survival (5 year DSS for cases 73% vs. controls 44%; p=0.0002). In the definitive analysis on the EOC cohort (61 cases, 178 controls) distribution of age, stage, optimal cytoreduction, serous histology and platinum chemotherapy remained similar amongst the cases and controls (p>0.05). Despite these similarities, cases had a significantly better survival (5 year DSS for cases 67% vs. controls 47%; p=0.007). On a multivariate analysis, metformin remained an independent predictor of survival (hazards ratio 3.7; 95% CI 1.6–9.0; p=0.002) after controlling for stage, grade, histology, chemotherapy, body mass index and surgical cytoreduction. Conclusion This study reports association rather than causation. Metformin intake was associated with better survival in ovarian cancer. Metformin is worthy of clinical trials in ovarian cancer.

Here, we investigate the potential role of the PARP inhibitor rucaparib (CO-338, formerly known as AG014699 and PF-01367338) for the treatment of sporadic ovarian cancer. We studied the growth inhibitory effects of rucaparib in a panel of 39 ovarian cancer cell lines that were each characterized for mutation and methylation status of BRCA1/2, baseline gene expression signatures, copy number variations of selected genes, PTEN status, and sensitivity to platinum-based chemotherapy. To study interactions with chemotherapy, we used multiple drug effect analyses and assessed apoptosis, DNA fragmentation, and γ H2AX formation. Concentration-dependent antiproliferative effects of rucaparib were seen in 26 of 39 (67%) cell lines and were not restricted to cell lines with BRCA1/2 mutations. Low expression of other genes involved in homologous repair (e.g., BCCIP, BRCC3, ATM, RAD51L1), amplification of AURKA or EMSY, and response to platinum-based chemotherapy was associated with sensitivity to rucaparib. Drug interactions with rucaparib were synergistic for topotecan, synergistic, or additive for carboplatin, doxorubicin or paclitaxel, and additive for gemcitabine. Synergy was most pronounced when rucaparib was combined with topotecan, which resulted in enhanced apoptosis, DNA fragmentation, and γH2AX formation. Importantly, rucaparib potentiated chemotherapy independent of its activity as a single agent. PARP inhibition may be a useful therapeutic strategy for a wider range of ovarian cancers bearing deficiencies in the homologous recombination pathway other than just BRCA1/2 mutations. These results support further clinical evaluation of rucaparib either as a single agent or as an adjunct to chemotherapy for the treatment of sporadic ovarian cancer.