Highlights of This Issue

Abstract

The topoisomerase I inhibitor irinotecan is used for the treatment of advanced colorectal cancer. However, a low proportion of patients show an objective response to irinotecan, and biomarkers capable of predicting response to irinotecan are needed. Dopeso and colleagues found that colorectal cancer patients with low Aprataxin tumor levels had significantly longer overall survival (OS) following irinotecan treatment, compared to patients with high Aprataxin levels. The difference in OS between the groups was almost 1.5 years. These results suggest that Aprataxin levels could be used alone or in combination with other markers to make informed decisions regarding patient treatment.Success in treating metastatic renal cell carcinoma (RCC) with T cell–based therapies has been limited. Here, Leisegang and colleagues identified a highly specific T-cell receptor (TCR) able to recognize an HLAA2–restricted antigen shared by more than 60% of RCCs, without recognizing normal cell counterparts. Transgenic expression of the TCR in recipient lymphocytes (i.e. from patients) allowed large numbers of T cells with tumor-specific cytotoxicity and polyfunctional cytokine secretion to be generated in a short time period. Due to its specificity, this reagent has the potential to advance immunotherapeutic treatment of metastatic RCC.Cyclooxygenase-2 (COX-2) is a key enzyme involved in cancer development and progression, and elevated COX-2 expression is related to unfavorable survival after radiotherapy. In this issue, Bi and colleagues show that the COX-2-1195G/A polymorphism, which results in increased COX-2 expression, is independently associated with poor survival among inoperable locally advanced non–small cell lung cancer (NSCLC) patients treated with chemoradiotherapy or radiotherapy alone. These results suggest that the COX-2-1195G/A polymorphism may help to optimize cancer treatment by identifying different responders to COX-2–targeted therapy.Gene amplifications of both ERBB2 and TOP2A have been reported in breast cancer. In this study, Brase and colleagues performed a systematic analysis of both markers by investigating correlations between DNA amplification, gene expression, and protein expression, as well as studying their prognostic and predictive relevance. They found that TOP2A RNA levels were significantly associated with the metastasis-free survival interval (MFI) and good response to anthracyclin-based therapy. In contrast, ERBB2 gene expression was associated with the MFI only in ER-positive carcinomas and showed no association with response to treatment. These results suggest that TOP2A RNA level is an appropriate marker for prognostic and predictive purposes.