Highlights of This Issue

Abstract

Microenvironmental factors may promote metastatic dissemination of Multiple Myeloma (MM) especially to the skeleton, causing bone destruction. In this study, Cocco and colleagues investigated whether IL-27 may function as an antitumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts. They found that human IL-27 directly inhibited MM cell growth both in vitro and in vivo primarily through inhibition of angiogenesis. IL-27 also damped the differentiation and activity of osteoclasts, and stimulated osteoblast proliferation. These findings demonstrate that IL-27 may block MM progression and metastatic bone resorption, and could open new approaches for MM therapy.SF2/ASF is a pre-mRNA splicing factor recently described as an oncoprotein. In this study, Ezponda and colleagues explored its relevance in non–small cell lung cancer (NSCLC). They found that SF2/ASF was upregulated in a high percentage of NSCLC tumors. Further, siRNA-mediated downregulation of SF2/ASF was found to promote survival of NSCLC cells by enhancing expression of survivin (an anti-apoptotic protein widely upregulated in cancer). Also, both SF2/ASF and survivin were implicated in lung cancer progression, as the combined expression of both factors was associated with poor prognosis.Cisplatin is a commonly prescribed chemotherapeutic agent that causes dose-limiting nephrotoxicity. Franke and colleagues evaluated the role of renal organic cation transporters (Oct1, Oct2) in cisplatin nephrotoxicity, as determined by urinary N-acetyl-β-D-glucosaminidase (NAG) activity. Cisplatin-treated Oct1/Oct2 knockout mice demonstrated increased survival and reduced nephrotoxicity. The Oct2 inhibitor cimetidine decreased cisplatin-induced NAG changes in wild-type mice to levels seen in knockout mice, but had no effect on OCT2 function in cancer cells. These results suggest that cimetidine can inhibit OCT2-mediated uptake of cisplatin in the kidney, and subsequently ameliorate nephrotoxicity with minimal effects on uptake in tumors.Targeting the anti-apoptotic BCL2 family is a promising area for anticancer drug development. One such inhibitor, ABT-263, has recently entered clinical trials in hematological malignancies, including chronic lymphocytic leukemia (CLL). Vogler and colleagues show that although ABT-263 is a potent inducer of apoptosis in CLL cells, it is less potent than the structurally related ABT-737 due to higher albumin binding. When tested in whole blood to mimic the in vivo situation, the activity of both inhibitors decreased ∼100-fold largely due to albumin binding. These results suggest that modification of ABT-263 may yield a BCL2-inhibitor with greater bioavailability and more favorable pharmacokinetics.