## 2 Liquid Biopsy and Its Utility in Skin Cancer Monitoring  
Liquid biopsy, a non or minimally invasive technique, is considered nowadays a revolutionary method capable of opening previously unexpected perspectives in the oncological and dermatological fields [27]. The most important advantage of this technique relies upon the possibility of relatively easy detection and isolation of several relevant biomarkers, such as circulating tumor cells (CTCs), circulating tumor DNA, and exosomes, compared to conventional tissue biopsy [28]. Due to recent technological and molecular advances, mainly in the microfluidic domain, the components obtained via liquid biopsy can now be more efficiently purified and analyzed [29].  
As skin cancer molecular profile is essential for a targeted therapeutic approach, the detection and isolation of tumor cells are mandatory in guiding the therapy. Although liquid biopsy is currently not completely adopted in daily clinical practice, it is still a useful modality of cell obtaining and subsequent characterization, especially when classic tissue biopsy is difficult to obtain or has led to unreliable results [30]. Several strong points of liquid biopsy make this technique appealing for clinical use, the most relevant characteristics compared to the classical approach being summarized in Table 1.  
One of the most important benefits of liquid biopsy is the possibility of serial monitoring. Samples can be prevailed at any time during patient therapy and follow-up, with the dynamic follow-up of tumor evolution (especially linked to the short half-life of ctDNA) being close to the principles of personalized medicine, when fine adjustments of drug therapy are advisable according to patient response. While initially, only the study of CTCs was possible from samples collected via liquid biopsy, it is possible now to perform an extended analysis of many components released by the tumor in body fluids (mainly blood). Cell-free circulating nucleic acids, such as DNA, mRNA, micro-RNA, and long non-coding RNA,  
\begin{table}
\begin{tabular}{c c} \hline \hline
**Liquid Biopsy** & **Tissue (Conventional) Biopsy** \\ \hline \multicolumn{3}{c}{**Advantages of liquid biopsy over conventional biopsy**} \\ \hline Easy to obtain (blood sample) & Most often easy to obtain (localization dependent) \\ Non- or minimally invasive & Invasive \\ Virtually no clinical complications & Low risk of complications (pain, bleeding, infection) \\ Possibility to highlight intra- and inter-tumor & Localized analysis (no intra- or inter-tumor heterogeneity \\ heterogeneity, and multiple tumor sites & Not applicable to serial monitoring \\ Applicable to serial monitoring & Not applicable to serial monitoring \\ Unmodified/fresh DNA study & Possibility of DNA study (possible technique-related DNA alterations) \\ \hline \hline \multicolumn{3}{c}{**Limitations of liquid biopsy compared to conventional biopsy**} \\ \hline Limited use in clinical practice & Currently gold standard approach \\ Utility under investigation & Limited histopathological analysis to CTCs & Histopathological analysis and staging \\ \hline \hline \end{tabular}
\end{table}
Table 1: Liquid biopsy versus tissue biopsy in skin cancers—advantages and limitations.  
are becoming of great importance, together with the study of \"tumor-educated platelets\" and vesicles, such as exosomes. In the next part, the authors focus mainly on the detection and characterization of the CTCs relevant to skin tumors, only briefly summarizing the emerging role of other components separated through liquid biopsy.