Highlights of This Issue

Abstract

The unique antigenic nature of chemically induced tumors is well established. In murine models, vaccination with 1 tumor provides protection from challenge with the same, but not other histologically identical tumors. Twitty and colleagues report that tumor-derived autophagosome vaccines, in contrast with whole-tumor vaccines, prime T cells with broader tumor-specific reactivity and provide significant cross-protection to challenge with similar tumors. Further, they show that ubiquitinated short-lived proteins, sequestered in autophagosomes in a p62-dependent fashion, contain the key antigenic components required for cross-protection. This strategy to broaden anticancer immunity is being explored in a clinical trial.Several recent clinical trials have shown successful results in the treatment of advanced thyroid cancer. All of the agents being evaluated in these trials are multikinase inhibitors targeting VEGF receptor 2 (VEGFR2) plus other receptor tyrosine kinases. Jin and colleagues report here on a preclinical study of a RAF inhibitor and a dual phosphoinositide 3-kinase (PI3) kinase/mTOR inhibitor that successfully inhibits 2 of the major downstream pathways of ras. Addition of the PI3 kinase inhibitor was effective even in BRAF mutant settings. This strategy may be a viable alternative to multikinase inhibitors in thyroid cancer.X-ray repair complementing defective repair in Chinese hamster cell 1 (XRCC1) protein is involved in DNA base excision and single strand break repair and may modulate chemoradiation outcomes by affecting efficient DNA damage repair. Ang and colleagues explored the relationship of XRCC1 protein expression with clinical outcomes in head and neck squamous cell carcinoma by immunohistochemistry. High XRCC1 expression was associated with poorer survival, particularly in patients undergoing chemoradiation. Furthermore, this association was independent of human papilloma virus status, clinical stage, and tumor primary site. Thus, patients with high XRCC1 expression before treatment may have poor outcomes from chemoradiation and may benefit from alternative management strategies.In vivo imaging of cellular proliferation with the biomarker [18F]fluorothymidine (FLT) and positron emission tomography has tremendous potential for monitoring treatment response in oncology. Wardak and colleagues investigated whether changes in tumor FLT kinetic parameters, assessed early after the start of therapy, could predict overall survival and progression-free survival in patients with recurrent high-grade glioma undergoing treatment with bevacizumab and irinotecan. They found that discriminant analysis of kinetic parameter changes could accurately classify patients into their known survival groups. This method could help physicians provide a personalized treatment regimen and thus improve patient outcomes.