Highlights of This Issue

Abstract

Concurrent chemoradiation is one of the widely used treatments for head and neck cancer, but it is often unsuccessful due to the development of chemo- and radioresistance. In this report, Yadav and colleagues demonstrate that sorafenib can enhance the therapeutic efficacy of chemoradiation treatment by sensitizing tumor cells via the downregulation of DNA repair proteins (ERCC-1 and XRCC-1) and also by decreasing tumor angiogenesis by blocking VEGF-mediated signaling. This strategy of combining low doses of sorafenib along with chemoradiation has the potential of significantly decreasing side effects associated with the current standard chemoradiation treatment while maintaining its therapeutic efficacy.The vasculature and blood flow in tumors are highly heterogeneous. The ability to image in real time the effects of antiangiogenic agents on vascular structure and function in tumors would greatly improve our knowledge on the mechanism of such agents and enable discovery of more effective ones. Zhang and colleagues have developed a new technology that enables variable-magnification in vivo fluorescence imaging as well as fluorescence tomography to visualize functional normalization of tumor blood vessels by antiangiogenic agents in real time. The results of this study also characterize the role of tumor vascular normalization in enhanced chemotherapeutic drug delivery and antitumor efficacy.A novel TRIM gene family member, TRIM59, was found to be upregulated in SV40 Tag oncogene-directed transgenic and knockout mouse prostate cancer (CaP) models. Two phosphorylated forms of TRIM59 were characterized to be correlated with tumorigenesis and the advanced CaP. Short hairpin RNA-mediated knockdown of TRIM59 caused S phase cell cycle and growth arrest, along with a hit-and-run effect implicating that the initial knockdown occurred early in the Ras signaling pathway. Transgenic mouse model upregulating the TRIM59 gene in the prostate revealed the proto-oncogenic activity in tumorigenesis and progression coincided with the upregulation of genes bridging between Ras and SV40Tag signaling pathways. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy of cancer.Drug resistance is the major cause of chemotherapy failure in ovarian cancer. De Souza and colleagues have shown that changes to the chemotherapy dosing schedule significantly affect drug resistance. Elimination of treatment-free intervals via continuous chemotherapy of the drug docetaxel resulted in greater antitumor efficacy than intermittent (once or three times weekly) dosing in chemosensitive and chemoresistant ovarian cancer models and did not induce upregulation of genes implicated in docetaxel resistance, whereas significant upregulation resulted from intermittent administration. This supports the clinical implementation of more frequent dosing schedules in the treatment of solid tumors such as ovarian cancer.