Highlights of This Issue

Preclinical animal models provide a key tool for non-invasive detection and quantitative measurement of long-term tumor burden. Here, Ramasamy and colleagues applied real-time non-invasive micro-CT imaging to demonstrate the therapeutic efficacy of silibinin in preventing lung tumor development through modulation of inducible nitric oxide synthase (iNOS). Micro-CT imaging revealed a significant and time-dependent decrease in the number and size of lesions in silibinin-treated wild-type animals, but not in iNOS‐/‐ mice. Further, CT results correlated with ex vivo tumor data measured at the end of the experiment. These results show the utility of micro-CT imaging in evaluating lung cancer chemopreventive agents.

B-cell chronic lymphocytic leukemia (B-CLL) is a common leukemia of adults. In this study, Zauli and colleagues evaluated the combination of Dasatinib (a multi-kinase inhibitor) plus Nutlin-3 (a nongenotoxic activator of the p pathway) in primary B-CLL patient cells and in B leukemic cell lines. They found that the drug combination induced synergistic cytotoxicity in both p53^wild-type and p53^{mutated/deleted} leukemic cells. Further, Akt down-regulation was found to be important in mediating the antileukemic activity of Dasatinib+Nutlin-3. These findings suggest that the combination of Dasatinib and Nutlin-3 represents an innovative therapeutic strategy for B-CLL.

TDiamond and colleagues performed a phase I clinical study of the Aurora and angiogenic kinase inhibitor ENMD-2076 in patients with advanced solid tumors. Antitumor activity was seen in several tumor types, including hepatocellular carcinoma, triple-negative breast cancer, and platinum-resistant ovarian cancer. ENMD-2076 exhibited both antimitotic and broad anti-angiogenic activity, and was tolerable up to 160 mg/m2 orally once daily with continuous dosing. Consistent with inhibition of the target kinases, doselimiting hypertension occurred. These findings support future clinical trials evaluating this agent, including an ongoing phase II study in platinumresistant ovarian cancer.

Tumor antigen NY-ESO-1 is a major target in human cancer vaccine studies, due to its tumor-restricted expression and strong immunogenicity. Here, Karbach and colleagues investigated the efficacy of NY-ESO-1 recombinant protein combined with the adjuvant CpG 7909 to prime antigen-specific naive B- and T-cells in prostate cancer patients. They observed induction of NY‐ESO‐1‐specific immune responses in a high proportion of NY‐ESO‐ 1‐naive patients (regardless of the level of NY-ESO-1 expression in the autologous tumor). These results demonstrate the strong immunogenicity of this vaccine formulation in vivo, and suggest that it may be effective in preventing the outgrowth of NY‐ESO‐1‐expressing cancers.