Chiara Nicolazzo ¹ Elisa Frullanti ^2,3 Paola Gazzaniga ^1* Maria Palmieri ^2,3

• ¹ Cancer Liquid Biopsy Unit, Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy, Rome, Italy
• ² Cancer Genomics and Systems Biology Lab, Department of Medical Biotechnology, University of Siena, Siena, Tuscany, Italy
• ³ Med Biotech Hub and Competence Center, Department of Medical Biotechnology, University of Siena, Siena, Tuscany, Italy

Cancer remains a leading cause of mortality worldwide and the field of oncology has seen significant advancements with the discovery and study of Circulating Tumor Cells (CTCs). First described more than 150 years ago (Ashworth TR, 1869), the CTC are released into the bloodstream from primary and metastatic tumors, potentially forming new tumors in distant organs. CTCs are critical components of liquid biopsies, offering a noninvasive and dynamic window into tumor biology. They provide invaluable insights into cancer dissemination, disease progression, and response to treatment, reflecting tumors spatial and temporal heterogeneity (Allen TA, 2024). A high CTC count has been associated with poor prognosis in several cancers and at various disease stages, especially in breast, lung, and prostate cancer and for this reason, to date, their use is mainly for prognostic purposes (Vasseur A, 2021).However, the potential of CTCs should not remain confined only to prognostic study but be extended also to clinical practice. Therefore, it is of pivotal importance to explore the clinical relevance of CTCs beyond their prognostic value, studying the emerging methods application for CTCs to use the information deriving from CTCs in the treatment of patients through precision therapy. The information provided by CTCs about genetic mutations, gene expression patterns, and biomarkers can be used to identify specific molecular targets for understanding drug resistance mechanisms and drug development, leading to personalized treatment options that can prevent metastasis and improve patient outcomes. This Research Topic focused on the recognition methods of CTCs based on deep learning and emerging tools to investigate the genome, transcriptome, proteome, and secretome of CTCs as biomarkers. In this special issue, two original research and three reviews have been published regarding new scientific advances in the CTCs. In particular, Chu X et al. study the potential of peptide magnetic nanoparticles (Pep@MNP) in capturing CTCs in pancreatic ductal adenocarcinoma. CTCs and CXCR4 expression were detected to explore their clinical significance. Indeed, the CXCR4+ CTCs were found to be associated with early recurrence and metastasis of PDAC. Therefore, CTCs identified by Pep@MNP detection system could be used as diagnostic and biomarkers of PDAC patients.