Issues

Deep sequencing of 2,860 long-term survivors of pediatric cancer identified accelerated clonal hematopoiesis (CH) and characterized STAT3 as a CH gene specific to Hodgkin lymphoma survivors.

Cancer cell genomic instability correlates with proinflammatory IL6 and IL8 production, VEGF, as well as regulatory T cells and is associated with primary resistance to immunotherapy and antiangiogenics in patients with advanced mesothelioma.

Focal amplicons via extrachromosomal DNA and intrachromosomal complex genomic rearrangements drive acquired MAPK inhibitor resistance, revealing nonhomologous end-joining DNA repair as key to their biogenesis and thereby DNA-PK_CS as a cotarget to prevent resistance.

High-resolution analysis of genomic rearrangements at human papillomavirus (HPV) integration sites reveals heterocateny, which implicates the capture, amplification, and recombination of host and viral DNA by HPV integration as its mechanism.

In small cell lung cancer, extrachromosomal DNAs (ecDNA) serve as MYC-amplifying units that contribute to disease heterogeneity as well as enable transcriptional flexibility that may promote the worse survival outcomes seen in tumors harboring ecDNA amplifications.

An antibody–drug conjugate (ADC) class that combines a novel self-immolative T moiety and the topoisomerase I inhibitor exatecan displays higher therapeutic indices to overcome intrinsic or induced tumor resistance to current ADCs while also improving ADC stability to limit off-target toxicities.

Tumor-associated microglia undergo oxidative stress to dysregulate orphan nuclear receptor NR4A2 signaling of SQLE-mediated cholesterol metabolism, offering synergistic vulnerabilities with immune checkpoint blockade therapy for glioblastoma.

Differences in the effects of LKB1 loss in human versus murine lung adenocarcinoma are attributed to differential TPI1 regulation that leads to divergent metabolic liabilities and has implications for therapeutic targeting in cancer.