The analysis of circulating tumor cells (CTCs) is an outstanding tool to provide insights into the biology of metastatic cancers, to monitor disease progression and with potential for use in liquid biopsy-based personalized cancer treatment. These goals are ambitious, yet recent studies are already allowing a sharper understanding of the strengths, challenges, and opportunities provided by liquid biopsy approaches. For instance, through single-cellresolution genomics and transcriptomics, it is becoming increasingly clear that CTCs are heterogeneous at multiple levels and that only a fraction of them is capable of initiating metastasis. It also appears that CTCs adopt multiple ways to enhance their metastatic potential, including homotypic clustering and heterotypic interactions with immune and stromal cells. On the clinical side, both CTC enumeration and molecular analysis may provide new means to monitor cancer progression and to take individualized treatment decisions, but their use for early cancer detection appears to be challenging compared to that of other tumor derivatives such as circulating tumor DNA. In this review, we summarize current data on CTC biology and CTC-based clinical applications that are likely to impact our understanding of the metastatic process and to influence the clinical management of patients with metastatic cancer, including new prospects that may favor the implementation of precision medicine. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Skin barrier damage after exposure to para-phenylenediamine Stratum corneum Stratum granulosum Stratum spinosum Stratum basale Para-phenylenediamine (PPD) Decreased expression of stratum corneum proteins and genes Disrup on of ght junc ons and decreased expression of ght junc on genes Non-responder hairdresser Allergic contact derma s pa ent Background: p-Phenylenediamine (PPD) is a strong contact allergen used in hair dye that is known to cause allergic contact dermatitis (ACD). Both private and occupational exposure to PPD is frequent, but the effect of PPD exposure in nonallergic occupationally exposed subjects is unknown. Objective: We sought to investigate the effects of PPD exposure on the skin of occupationally exposed subjects with and without clinical symptoms. Methods: Skin biopsy specimens were collected from 4 patients with mild and 5 patients with severe PPD-related ACD and 7 hairdressers without contact dermatitis on day 4 after patch testing with 1% PPD in petrolatum. RNA sequencing and transcriptomics analyses were performed and confirmed by using quantitative RT-PCR. Protein expression was analyzed in skin from 4 hairdressers and 1 patient with ACD by using immunofluorescence staining.

<p>List of recurrent mutations</p>