A method for parallel sequencing of single-cell extrachromosomal circular DNA (ecDNA) and full-length mRNA transcriptomes has enabled new insights into the roles of ecDNA in cancer progression, researchers from Charité hospital and the Max Delbrück Center for Molecular Medicine reported in Nature Genetics on May 8, 2023. Circular DNAs are present in at least a third of cancer cells, and their presence correlates with poor prognosis in many cases. They can carry driver genes that have separated themselves from their chromosome of origin, and some research suggests that they serve as “reserve copies” of driver genes. Boundless Bio Inc. is in phase I trials targeting ecDNAs.
A pill that delivers electrical stimulation to the vagus nerve from inside the stomach was able to trigger the release of appetite-controlling neurohormones, specifically the “hunger hormone” ghrelin. The work, which was described in the April 26, 2023, issue of Science Robotics, could pave the way for treating “metabolic, [gastrointestinal], and neuropsychiatric disorders noninvasively with minimal off-target effects,” the authors wrote in their paper.
A pill that delivers electrical stimulation to the vagus nerve from inside the stomach was able to trigger the release of appetite-controlling neurohormones, specifically the “hunger hormone” ghrelin.
Researchers have identified a druggable pocket on the phosphatase Wip1, which regulates the tumor suppressor TP53 as well as DNA damage repair proteins. The work, which was published in Frontiers in Molecular Biosciences on April 18, 2023, by researchers from the University of Pennsylvania, could lead to therapeutics targeting Wip1. And the computational deep learning methods used to identify the pocket are broadly useful for identifying what the authors call “cryptic” pockets.
Antitumor immunotherapy has notched big wins, but in a small proportion of patients. And one possible explanation for why is that approved immunotherapies are not yet planting their flag on most of the battlefields where tumors and the immune system engage in combat. At the opening AACR 2023 plenary session, Ralph DeNardo celebrated the successes of the current, mostly T-cell-based approaches, but also encouraged his colleagues to think more broadly about the antitumor immunity.
Combining the personalized cancer vaccine mRNA-4157 (V-940, Moderna Inc.) with Keytruda (pembrolizumab, Merck & Co. Inc.) significantly extended recurrence-free survival in patients with stage III/IV resected high-risk melanoma in the randomized phase II KEYNOTE-942/mRNA-4157-P201 trial. Compared to Keytruda alone, adding the vaccine cut the risk of recurrence or death by 44% 18 months after treatment, lead investigator Jeffrey Weber reported at the opening clinical trials plenary of the 2023 annual meeting of the American Association for Cancer Research (AACR).
Heterogeneity, in both tumors and their microenvironment, limits the success of current cancer treatments. But it also provides opportunities. Heterogeneities “are not barriers to therapy, they are vulnerabilities to be exploited,” was how David DeNardo described his take at the 2023 annual meeting of the American Association for Cancer Research (AACR) on Sunday.
Researchers have gained new insights into physiological mechanisms that protect against blood clotting in immobilized individuals by studying animals that stay immobile for a good chunk of the year at a time: hibernating bears. “As a clinician, if you think about immobility, you always think about thrombosis,” Tobias Petzold told BioWorld. But his team’s work, which was published in the April 13, 2023, issue of Science, demonstrated that “immobility can trigger antithrombotic mechanisms.”
Helicobacter pylori infection and germline genetic variants interacted with each other to affect the risk of gastric cancer in a study comparing more than 11,000 patients with stomach cancer and 44,000 people without cancer. Researchers from the RIKEN Center for Integrative Medical Sciences (IMS) published those findings in the March 30, 2023, issue of the New England Journal of Medicine.
If its challenges can be overcome, radioligand therapy is poised to change the way many cancers are treated. It is also likely to become an example of how scientific advances, once they are translated successfully, can enable further insights in a bench-to-bedside-to-bench loop. David Piwnica-Worms, professor and chair of cancer systems imaging at The University of Texas MD Anderson Cancer Center, predicted that as radioligand therapy expands, many questions will be answered about both radiation biology and the interaction of radiation with the immune system more specifically.
