Highlights of This Issue

Abstract

Doxorubicin is among the most effective anticancer drugs. Yet, a significant number of patients develop cardiotoxicity, for which identification of predicting factors remains a clinical challenge. Here, Khiati and colleagues demonstrate that mitochondrial topoisomerase, Top1mt, is critical to avoid cardiotoxicity. Top1mt knockout mice are hypersensitive to doxorubicin, and die from cardiac failure with mitochondrial DNA (mtDNA) loss and severe mitochondrial and cardiomyocyte abnormalities. The study demonstrates the importance of mtDNA homeostasis for doxorubicin tolerance and suggests the relevance of testing genomic variants for TOP1mt and others mitochondrial genes in doxorubicin-treated patients.Recent progress of immunotherapy has led to the development of many novel immune modulators and vaccines. With the potential number of different combinations, there is an urgent need to revisit the feasibility of the traditional phase 1 dose escalation design in early cancer vaccine development. Rahma and colleagues reviewed over 200 phase I/II cancer vaccine studies showing a lack of correlation between dose escalation and toxicities or cellular immune response. In addition, the authors described a novel design to identify the safe and immune active dose in cancer vaccines without the need to enroll a large number of patients.Circulating tumor cells (CTCs) expressing EpCAM is an independent prognostic factor recurrence in HCC patients. To comprehensively investigate the clinical significance of these cells in HCC patients undergoing different treatment, Guo and colleagues established a novel optimized negative enrichment and qRT-PCR-based CTC detection platform with high sensitivity, specificity, reproducibility, and a small sample volume requirement and discovered that EpCAM mRNA-positive CTCs serve as a novel indicator for the risk of recurrence or progression in HCC patients and a promising surrogate tool for surveillance of the therapeutic response instead of radiologic scans with the benefits of increased convenience and safety.MET amplification is one of the mechanisms underlying resistance to EGFR TKIs in NSCLC. Noninvasive imaging of proliferation with 3′-deoxy-3′-[18F]-fluorothymidine ([18F]FLT) and PET was used to detect MET-mediated resistance in NSCLC and to monitor its reversal by MET inhibitors. Iommelli and colleagues showed that the persistently high uptake of [18F]FLT in tumors after treatment with EGFR TKIs identified resistance, whereas the significant reduction of tracer uptake in response to treatment with MET inhibitors indicated the reversal of MET-mediated resistance. The major clinical implication of the study is to provide an adaptive imaging biomarker for personalized targeted therapy in NSCLC patients.