Axitinib Induces Senescence in Endothelial Cells via ROS and ATM; Stanford Identifies Key Cancer-Associated Genetic Variants; Microsatellite Mutations as Cancer Molecular Clocks

Axitinib, a drug, induces senescence [sen-es-uhns] (cellular aging) in endothelial cells (cells lining blood vessels) through reactive oxygen species (ROS) [ar-o-es] and ATM (Ataxia Telangiectasia Mutated) kinase [uh-tax-ee-uh tel-an-jee-ek-tay-zhuh myoo-tay-ted]. A short exposure to Axitinib triggers senescence in human umbilical vein endothelial cells (HUVECs) [eych-yoo-vek] with increased SA-β-gal [es-ay-beta-gal] expression, a marker of cellular senescence. The percentage of blue, SA-β-gal-positive cells, increased progressively in a time-dependent manner. This process involves ROS accumulation and ATM phosphorylation [fos-for-uh-lay-shun], but not DNA damage. N-Acetyl-Cysteine (NAC) [en-uh-see-til-sis-teen], an antioxidant, and KU-55933 [kay-yoo-fife-fife-thri-thri], an ATM kinase inhibitor, prevent Axitinib-induced senescence. Researchers at Stanford University identified nearly 400 single nucleotide variants (SNVs) [es-en-vees] in inherited DNA crucial for cancer initiation and progression. These variants affect DNA damage repair, cellular energetics, and cell interactions. The research used massively parallel reporter assays to analyze the impact of numerous genetic variants simultaneously. The findings could inform novel genetic screening tools for cancer risk assessment. A study in Nature Genetics shows that mutations in guanine homopolymer microsatellites [gwah-neen ho-moh-pol-ih-mer mahy-kroh-sat-uh-lites] serve as accurate molecular clocks in cancer. These mutations, arising during DNA synthesis due to DNA polymerase slipping, reveal the number of cell divisions during cancer development and progression. This method provides a direct and precise indicator of replication events, robust to confounding mutational processes. Cancer phylogenetic trees [fahy-loh-jen-et-ik trees] describe the evolutionary relationship between primary tumors and metastatic sites [met-uh-stat-ik sites].