The 14-3-3 family proteins are phosphoserine/phosphothreonine binding proteins constituting a conserved class of proteins which are detected in all eukaryotic cells. In mammalians, 14-3-3 proteins have seven distinct isoforms (β, γ, ε, η, ζ, σ and τ/θ) which are involved in various cellular processes including signal transduction, cell cycle, cell proliferation, apoptosis, differentiation and survival. 14-3-3 proteins do not have a distinct catalytic activity and often regulate the activity, stability, subcellular localization and interactions of other proteins. The 14-3-3 family proteins function through interacting with their client proteins or facilitating the interaction of other proteins likely as adaptor proteins. The versatile functions of these proteins in the regulation of cell growth, cell division, cell death and cell migration make them candidate proteins for which an important role in cancer development could be envisioned. Indeed, analysis of cancer cell lines and tumor-derived tissues have indicated the differential abundance or post-translational modification of some 14-3-3 isoforms. In this review, we aimed to show how deregulation of 14-3-3 proteins contributes to initiation, establishment and progression of cancers with a particular emphasis on lung cancer. The role of these proteins in cancer-relevant processes including cell cycle, cell migration, cell-cell communication and programmed cell death will be discussed in detail.

The concept of liquid biopsy as an analysis tool for non-solid tissue carried out for the purpose of providing information about solid tumors was introduced approximately 20 years ago. Additional to the detection of circulating tumor cells (CTCs), the liquid biopsy approach quickly included the analysis of circulating tumor DNA (ctDNA) and other tumor-derived markers such as circulating cell-free RNA or extracellular vesicles. Liquid biopsy is a non-invasive technique for detecting multiple cancer-associated biomarkers that is easy to obtain and can reflect the characteristics of the entire tumor mass. Currently, ctDNA is the key component of the liquid biopsy approach from the point of view of the prognosis assessment, prediction, and monitoring of the treatment of non-small-cell lung cancer (NSCLC) patients. ctDNA in NSCLC patients carries variants or rearrangements that drive carcinogenesis, such as those in EGFR, KRAS, ALK, or ROS1. Due to advances in pharmacology, these variants are the subject of targeted therapy. Therefore, the detection of these variants has gained attention in clinical medicine. Recently, methods based on qPCR (ddPCR, BEAMing) and next-generation sequencing (NGS) are the most effective approaches for ctDNA analysis. This review addresses various aspects of the use of liquid biopsy with an emphasis on ctDNA as a biomarker in NSCLC patients.