Hyperprogressive disease: A distinct pattern of progression to immune checkpoint inhibitors.

Hyperprogressive disease (HPD) is a novel pattern of progression attributed to immune checkpoint inhibitor (ICI) treatment and characterized by a dramatic tumor surge and poor survival. The concept of HPD is still controversial, while the definition varies widely across studies. Although HPD has been associated with multiple clinicopathological and molecular features, there is no biomarker to predict this detrimental effect of immunotherapy and the underlying mechanism remains unknown. The aim of this comprehensive review is to summarize current data on HPD and present the controversies and clinical care management challenges for oncologists treating patients with ICIs.

Utilizing nullomers in cell-free RNA for early cancer detection.

Early detection of cancer can significantly improve patient outcomes; however, sensitive and highly specific biomarkers for cancer detection are currently missing. Nullomers are the shortest sequences that are absent from the human genome but can emerge due to somatic mutations in cancer. We examine over 10,000 whole exome sequencing matched tumor-normal samples to characterize nullomer emergence across exonic regions of the genome. We also identify nullomer emerging mutational hotspots within tumor genes. Finally, we provide evidence for the identification of nullomers in cell-free RNA from peripheral blood samples, enabling detection of multiple tumor types. We show multiple tumor classification models with an AUC greater than 0.9, including a hepatocellular carcinoma classifier with an AUC greater than 0.99.