BRCA Mutation and Outcome in Recurrent Ovarian Cancer
Safra et al., Page 2000
Germline mutations in BRCA1 or BRCA2 tumor suppressor genes are found in approximately 10% of epithelial ovarian cancers (EOC). Patients with BRCA mutations (BRCA +) benefit from platinum-based treatment more than non-carriers due to the increased chemosensitivity that is related to the impaired ability to repair DNA by homologous recombination. Using a retrospective comparison of patients who were BRCA + or deemed nonhereditary, this trial investigated whether BRCA + predicts improved outcome following pegylated liposomal doxorubicin (PLD) for recurrence. In this retrospective analysis, recurrent EOC BRCA mutation carriers treated with PLD had an improved outcome, which appeared to be independent of platinum sensitivity.
Axl and Mer in Cancer
Verma et al., Page 1763
The mammalian TAM receptor tyrosine kinase family (RTK) includes three closely related members: Tyro-3, Axl, and Mer. Abnormal expression and ligand-induced activation of Axl or Mer can provide a survival advantage in a variety of cancers. Inhibition of Axl and Mer may enhance the sensitivity of cancer cells to cytotoxic agents and could potentially be a therapeutic strategy in targeting cancer cells. Verma and colleagues review the role of Axl and Mer in normal cellular function, their role in oncogenesis, and the potential to inhibit these RTKs as therapeutic strategies in treatment of cancer.
miRNA Target-Dysregulated Network
Xu et al., Page 1857
MicroRNA (miRNA) roles in tumor biology remain largely unknown. Xu and colleagues introduce a systems biology approach based on the miRNA-target dysregulated network (MTDN) in specific tumor phenotypes to prioritize disease miRNAs. The MTDN is constructed by combining miRNA-target interactions with miRNA and mRNA expression profiles in tumor and nontumor tissues. Xu and colleagues' model achieves higher accuracy for classifying prostate cancer from NPC miRNAs in its application to prostate cancer. Predicted prostate cancer miRNAs are closely associated with oncogenesis, and miRNAs within families or from different families show combinatorial dysregulation of target genes. Finally, three miRNA target regulations are verified to hold in prostate cancer cells by transfection assays.
ABT-898 Induces Tumor Regression in Ovarian Cancer
Campbell et al., Page 1876
Epithelial ovarian cancer is the most lethal gynecologic malignancy and often is not detected until late stages where current treatment modalities have limited effectiveness. Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis and reduced expression is often associated with aggressive tumor growth. In this paper, Campbell and colleagues show that the TSP-1 mimetic peptide ABT-898 was able to induce regression of advanced-stage ovarian tumors, cause destruction of abnormal tumor blood vessels, and significantly prolong survival. TSP-1 shows promise as an important tool in the treatment of advanced stage ovarian cancer.