Highlights of This Issue

Abstract

c-Myc, as the central hub for cellular signals, is deregulated at multiple levels in almost all human cancers. Although this makes c-Myc an attractive candidate target for cancer therapy, drug development against c-Myc has been challenging. Fan-Minogue and colleagues have identified the new antineoplastic function of an antiparasitic agent, nitazoxanide, through their robust cell-based high throughput screening system by utilizing a c-Myc activation sensor. This new system allows large-scale and fast screening for compounds inhibiting c-Myc, thus potentially accelerating drug development against c-Myc–associated cancer.Aberrant activity of receptor tyrosine kinases has been associated with tumor progression in a wide variety of human malignancies. In the present study, Burbridge and colleagues demonstrate that S49076, a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3, has specific targeting and strong antitumor effect in vitro and in vivo. S49076 not only showed synergy with bevacizumab in colon cancer xenograft models but also blocked the growth of bevacizumab-resistant tumors. A phase I clinical trial of S49076 is currently underway in patients with advanced solid tumors.Hypoxia is a critical microenvironmental factor in multiple myeloma. It has been shown previously that the hypoxia-activated prodrug TH-302 selectively targets hypoxic multiple myeloma cells. To further explore the application of TH-302 in multiple myeloma, Hu and colleagues evaluated in this study the antitumor effect of TH-302 in combination with the proteasome inhibitor bortezomib, which is already approved for multiple myeloma. The combination of TH-302 and bortezomib was found to synergistically induce apoptosis in human multiple myeloma cell lines in vitro and prolong the survival of 5T33MMvv multiple myeloma mice in vivo. This study provides a rationale for clinical evaluation of this combination in multiple myeloma patients.Patients with glioblastoma have an exceptionally grim prognosis. Although HER1/EGFR is the most frequently amplified oncogene in this disease, monotargeted agents against this receptor have fallen short of improving the clinical course. In order to increase the efficacy of HER1/EGFR inhibition, Karpel-Massler and colleagues screened rationally identified candidate molecular targets and found that combining NSC23766, an inhibitor of RAC1, with erlotinib results in a synergistic antiproliferative effect on primary and established glioblastoma cells. This novel therapeutic approach might be promising in developing a more efficient treatment for glioblastoma patients.