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Circulating Tumor Cells in Oncology: From Liquid Biopsy to Clinical Decision-Making

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 25 November 2025 | Viewed by 570

Special Issue Editor

Special Issue Information

Dear Colleagues,

Cancer remains one of the leading causes of death worldwide. Despite significant advances in diagnostics and therapeutics, tissue biopsy continues to be the gold standard for cancer diagnosis and treatment planning. However, the limitations of this approach have become increasingly evident, particularly due to intratumoral heterogeneity, which can compromise the accuracy and representativeness of tissue-based assessments.

In this context, liquid biopsy is emerging as a promising, minimally invasive tool for precision oncology. Among its components, circulating tumor cells (CTCs) are gaining considerable attention for their potential to provide real-time insights into tumor dynamics. Since CTCs actively participate in the metastatic process, they offer clinically relevant information at the protein, RNA, and DNA levels.

Although several innovative approaches have been developed for the isolation and characterization of CTCs, significant technical and biological challenges remain. These include improving detection sensitivity, understanding the mechanisms governing their survival in the bloodstream, and deciphering the interactions between CTCs and blood immune cells. Moreover, the in vitro culture of CTCs represents a powerful strategy to explore their molecular features and functional properties more deeply.

The goal of this Special Issue is to highlight recent advances in CTC-based analyses across various cancer types, with a focus on their role in identifying novel diagnostic and prognostic biomarkers and in deepening our understanding of tumor biology. We welcome original research articles and reviews that explore the molecular mechanisms underlying CTC behavior and their integration into clinical workflows. Emphasis will be placed on how CTCs can support patient stratification, guide therapeutic decisions, and help overcome treatment resistance, ultimately contributing to the advancement of personalized cancer medicine.

We look forward to your valuable contributions to this Special Issue.

Dr. Maria Beatrice Morelli
Guest Editor

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Keywords

  • circulating tumor cells (CTCs)
  • liquid biopsy
  • cancer biomarkers
  • precision oncology
  • metastasis
  • cancer diagnostics
  • cancer prognosis
  • CTC enrichment
  • CTC isolation techniques
  • single-cell analysis
  • tumor microenvironment
  • CTC culture
  • immune surveillance
  • blood-based biomarkers
  • molecular profiling
  • CTC-derived cell lines
  • treatment resistance
  • personalized cancer therapy
  • cell reprogramming
  • anti-tumor immunity

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Published Papers (1 paper)

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Research

13 pages, 1249 KB  
Article
Dynamics of Telomerase-Based PD-L1 Circulating Tumor Cells as a Longitudinal Biomarker for Treatment Response Prediction in Patients with Non-Small Cell Lung Cancer
by Issei Sumiyoshi, Shinsaku Togo, Takahiro Okabe, Kanae Abe, Junko Watanabe, Yusuke Ochi, Kazuaki Hoshi, Shoko Saiwaki, Shuko Nojiri, Yuichi Fujimoto, Yukiko Namba, Yoko Tabe, Yasuo Urata and Kazuhisa Takahashi
Int. J. Mol. Sci. 2025, 26(19), 9583; https://doi.org/10.3390/ijms26199583 - 1 Oct 2025
Viewed by 390
Abstract
Noninvasive liquid biopsy for monitoring circulating tumor cells offers valuable insights for predicting therapeutic responses. We developed TelomeScan® (OBP-401), based on the detection of telomerase activity as a universal cancer cell marker and an indicator of the presence of viable circulating tumor [...] Read more.
Noninvasive liquid biopsy for monitoring circulating tumor cells offers valuable insights for predicting therapeutic responses. We developed TelomeScan® (OBP-401), based on the detection of telomerase activity as a universal cancer cell marker and an indicator of the presence of viable circulating tumor cells (CTCs) for patients with advanced non-small cell lung cancer (NSCLC). This system evaluated CTC subtypes characterized by programmed death ligand 1 (PD-L1), an immune checkpoint molecule, and vimentin, an epithelial–mesenchymal transition (EMT) marker, using a multi-fluorescent color microscope reader. The prognostic value and therapeutic responses were predicted by dynamically monitoring CTC counts in 79 patients with advanced NSCLC. The sensitivity and specificity values of TelomeScan® for PD-L1(+) cells (≥1 cell) were 75% and 100%, respectively, indicating high diagnostic accuracy. PD-L1(+) and EMT(+) in CTCs were detected in 75% and 12% of patients, respectively. Detection of PD-L1(+)CTCs and PD-L1(+)EMT(+) CTCs before treatment was associated with poor prognosis (p < 0.05). Monitoring of reducing and increasing PD-L1(+) CTC counts in two sequential samples (baseline, cycle 2 treatment) correlated significantly with partial response (p = 0.032) and progressive disease (p = 0.023), respectively. Monitoring PD-L1(+)CTCs by TelomeScan® will aid in anticipating responses or resistance to frontline treatments, optimizing precision medicine choices in patients with NSCLC. Full article
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