Longitudinal liquid biopsy predicts clinical benefit from immunotherapy in advanced non-small cell lung cancer.

High heterogeneity in clinical benefit characterizes the use of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). We prospectively enrolled 113 advanced NSCLC patients treated with ICIs and performed liquid biopsy at the time of ICI start (T1), after 3 weeks (T2) and at the time of radiological evaluation (T3). Molecular variables were associated with outcome endpoints: cfDNA quantification, its dynamic change (∆T2-T1), variant allele frequency (VAF) of the gene with the highest frequency detected at baseline with NGS (maxVAF) and its dynamic change (∆T2-T1).

Anti-VEGF therapy selects for clones resistant to glucose starvation in ovarian cancer xenografts.

Background: Genetic and metabolic heterogeneity are well-known features of cancer and tumors can be viewed as an evolving mix of subclonal populations, subjected to selection driven by microenvironmental pressures or drug treatment. In previous studies, anti-VEGF therapy was found to elicit rewiring of tumor metabolism, causing marked alterations in glucose, lactate ad ATP levels in tumors. The aim of this study was to evaluate whether differences in the sensitivity to glucose starvation existed at the clonal level in ovarian cancer cells and to investigate the effects induced by anti-VEGF therapy on this phenotype by multi-omics analysis.

Detection of Low-Frequency Mutations in cfDNA From -Mutated NSCLC Patients After First-Line EGFR Tyrosine Kinase Inhibitors.

Background: Molecular profiling of advanced mutated NSCLC has recently demonstrated the co-existence of multiple genetic alterations. Specifically, co-existing -mutations in NSCLCs have been described, despite their prevalence at progression and their role in the response to tyrosine kinase inhibitors (TKIs) remain marginally explored. Aim of our study was to investigate the prevalence of co-existing mutations at the time of progressive disease and explore their impact on clinical outcome.