Highlights of This Issue

Abstract

Suppression of cellular immunity has long been observed in patients with glioblastoma. Sippel and colleagues provide evidence for activation of circulating neutrophils in patients with glioblastoma associated with increased release of the immunosuppressive enzyme Arginase I (ArgI). In vitro targeting of ArgI resulted in restoration of T-cell function in patients with glioblastoma, providing an intriguing new target for clinical intervention designed to restore cellular immune function in this population.Adhesion of circulating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. In this study, Barrow and colleagues revealed that serum levels of several galectin members were greatly increased in colon and breast cancer patients and promoted cancer-endothelial adhesion by interaction with cancer-associated Thomsen-Friedenreich/mucin 1 protein (TF/MUC1). Elevated circulating galectin-2 levels were associated with increased mortality in cancer patients, but this association was suppressed when auto–anti-MUC1 antibodies with specificity for the TF epitope were also present in the circulation. Thus, increased circulation of several galectin members is common in cancer patients and promotes circulating cancer cell metastatic spreading. Targeting the actions of circulating galectins may therefore represent a promising therapeutic approach to reduce metastasis.Accumulating evidence has demonstrated that tumor-initiating cells (T-IC) are resistant to chemotherapy. Zhu and colleagues demonstrated that mir-128 was significantly reduced in breast T-ICs, with the overexpression of its targets Bmi-1 and ABCC5, which regulated the chemotherapeutic resistance. Furthermore, miR-128 reduction in breast cancer tissues was correlated with chemoresistance and poor survival in patients with breast cancer. These findings imply that examination of miR-128 expression is valuable in predicting patient survival and therapeutic response in breast cancer and provide the basis for developing a combined strategy using miR-128 mimics and chemotherapy.Dysregulated c-MET signaling plays important roles in many cancers and represents an attractive therapeutic target. Liu and colleagues discovered a highly selective and potent c-MET kinase inhibitor, INCB28060. INCB28060 effectively inhibits c-MET–dependent signaling and neoplastic activity in various preclinical models. Furthermore, c-MET upregulates epidermal growth factor receptor and HER3 activity through interaction with these receptors and/or by inducing their ligands, and this activity can be reversed by INCB28060. Although numerous c-MET pathway inhibitors are being developed, they may have limitations in their potency, selectivity, pharmacokinetics, safety profile, or mechanisms of action. The properties shown by INCB28060 may enable this agent to overcome these limitations and allow for assessment of the therapeutic potential of c-MET pathway inhibition.