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Liquid biopsy LBx provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution. The Augsburg Longitudinal Plasma Study ALPS is a prospective trial for patients with metastatic cancer that comprises sequential collection of LBx samples, tumor tissue, radiological imaging data, clinical information and patient-reported outcomes.
From April to October , patients have been enrolled. On average, First CAPP-seq analyses in 60 patients comprised samples and demonstrated a detection sensitivity of 0. Advances in molecular tumor diagnostics have dramatically improved the functional understanding of oncogenesis and enabled comprehensive molecular characterization of many different types of cancer [ 1 ], [ 2 ], [ 3 ], [ 4 ]. As a result, new predictive biomarkers have been identified and targeted anticancer drugs have been developed.
Today, more than 80 targeted cancer therapies have been approved by the U. Food and Drug Administration FDA for the treatment of solid malignancies, approximately half of which are linked to specific predictive biomarkers, enabling personalized cancer treatment [ 5 ]. However, the molecular mechanisms underlying response and acquisition of resistance are still incompletely understood [ 6 ].
Predictive biomarkers rely almost exclusively on genomic profiles obtained from pre-therapeutic tissue biopsies TBx and therefore depend on sample availability and sufficient quality. Moreover, they are susceptible to sampling biases arising from intraindividual or even intralesional spatial heterogeneity [ 6 ], [ 7 ], [ 8 ].
Tumor cells have the potential of adapting to the novel environment provided by the treatment and its selective pressure. Consequently, individual cells may develop resistance mechanisms over time [ 9 ].