Highlights of This Issue

Abstract

Breast cancer remains the leading cause of cancer-related death among women worldwide. Modifiable dietary components, such as coffee, may influence breast cancer and treatment responses. In a translational study, Rosendahl and colleagues uncovered associations between coffee consumption and tumor characteristics in breast cancer patients, as well as longer disease-free survival among tamoxifen-treated patients. Mechanistically, this was linked to altered estrogen- and insulin-like growth factor I receptor levels and downstream signaling, resulting in impaired cell-cycle progression and enhanced cell death. An improved understanding of how coffee can influence breast cancer and treatment response may yield more evidence-based lifestyle recommendations during treatment.It has long been advocated that normalization of peritumoral vessels through vascular endothelial growth factor (VEGF) inhibition may help to improve cytotoxic drug delivery to tumors. The best timing of giving VEGF inhibitor, however, remains unknown. In this clinical trial, Lu and colleagues tackled this issue by administrating bevacizumab one day before the combination of etoposide and cisplatin (BEEP regimen) to breast cancer patients whose metastatic brain tumors were refractory to whole brain radiotherapy. The BEEP regimen showed a central nervous system response rate of 77.1% by volumetric criteria and was associated with manageable toxicities.The pediatric tumor neuroblastoma presents with extraordinarily heterogeneous clinical courses, ranging from spontaneous regression to fatal disease progression. Accurate assessment of each individual patient's risk is therefore essential to appropriately tailor therapeutic intensities. To improve treatment stratification, Oberthuer and colleagues determined gene expression profiles of 709 primary neuroblastomas by microarrays and developed a gene expression-based classifier that predicts patient outcome with unprecedented precision. They developed a novel risk assessment system that combines the classifier with established markers, which may avoid over- and under-treatment of future neuroblastoma patients.Analyzing multiple tumor regions, Friemel and colleagues demonstrate intratumor heterogeneity in the majority of treatment-naïve hepatocellular carcinomas (HCC). Intratumor heterogeneity was not restricted to morphological features, immunohistochemical markers, or mutational aberrations of critical driver genes, CTNNB1 and TP53, but hierarchically linked between all three. The emergence of intratumor heterogeneity highlights the challenges associated with molecular classification of HCC and the development of targeted therapies because distinct HCC subpopulations may foster tumor adaptations resulting in therapy resistance or evasion.