Highlights of This Issue

Abstract

Chemotherapy is used to treat metastatic/recurrent nasopharyngeal carcinoma (NPC), but there is a need for reliable biomarkers to predict treatment outcome early. Wang and colleagues explored the role of Epstein-Barr virus (EBV) clearance rate by quantifying serial changes of circulating EBV DNA concentration in NPC patients undergoing chemotherapy. They found that the rate of EBV clearance within the first month of treatment reflects chemosensitivity and predicts tumor response and patient survival. These results suggest that clearance of EBV DNA could be used as an early tumor response marker, and NPC patients with a slow plasma EBV DNA clearance rate may be considered for a chemotherapy regimen change.Cancer stem cell (CSC)–targeted therapeutic interventions, such as immunotherapy, hold promise for treatment of human cancers. Di Tomaso and colleagues performed an immunobiological characterization of a large panel of glioblastoma multiforme (GBM) CSC lines and paired non-CSC lines cultured in FBS. They found that T-cell responses against CSCs pretreated with IFN-γ could be induced in vitro. Notably, CSCs, but not autologous FBS-cultured cells, could inhibit allogeneic T-cell proliferation. These results could help to identify GBM patients with CSCs that can be targeted by immunotherapy.Mechanism-driven drug discovery relies on a thorough validation of molecular targets whose inhibition selectively kills cancer cells with a minimal effect on normal cells. In this study, Jia and colleagues identified and validated the SCF E3 ubiquitin ligase component SAG as a novel anticancer and radiosensitizing target. They found that SAG is overexpressed in a number of human primary cancers, and that silencing SAG with siRNA selectively kills cancer cells and sensitizes radioresistant cancer cells. Thus, development of small molecule inhibitors or RNAi-based therapy targeting SAG is a promising cancer treatment strategy.GMX1777 is a novel inhibitor of nicotinamide phosphoribosyl-transferase, an enzyme involved in NAD biosynthesis. Kato and colleagues used in vitro and in vivo models of head and neck cancer (HNC) to show that GMX1777 can enhance radiation efficacy via interference with DNA repair and tumor angiogenesis. Further, FDG-PET imaging corroborated the metabolic shutdown in these tumors. This study illustrates a potential therapeutic opportunity in targeting tumor metabolism, and suggests that GMX1777 plus radiotherapy warrants further clinical evaluation in patients with HNC.