Abstract

Liquid Biopsy: Detection and Molecular Characterization of Circulating Tumor Cells and DNA

Klaus Pantel, Professor and Founding Director, University Of Hamburg

Circulating tumor cells (CTCs) are usually detected by immunological or RT-PCR assays (Alix-Panabieres & Pantel, Nature Rev Cancer 2014). Most CTC assays rely on epithelial markers and miss CTCs undergoing an epithelial-mesenchymal transition (EMT). New markers such as the actin bundling protein plastin-3 (Yokobori et al., Cancer Res. 2013) are not downregulated during EMT and not expressed in normal blood cells might overcome this important limitation and, therefore, increase the sensitivity of CTC assays. CTC enumeration and characterization provides reliable information on prognosis and may serve as liquid biopsy (Alix-Panabieres & Pantel, Clin. Chem. 2013; Pantel; Alix-Panabieres, Cancer Res., 2013). Functional characterization using specialized in vitro and in vivo test systems has started (Bacelli et al, Nat. Biotech. 2013; Hodgkinson et al, Nat. Med. 2014; Cayrefourcq et al., Cancer Res. 2015). Moreover, monitoring of CTCs before, during and after systemic therapy (e.g., chemotherapy, hormonal therapy, antibody therapy) and determination of therapeutic targets (e.g., PD-L1, Mazel et al., Mol. Oncol. 2015) might serve as surrogate marker for response to therapy. Besides CTCs the analysis of ctDNA and circulating microRNAs may provide complementary information as “liquid biopsy” (Pantel; Alix-Panabieres, Cancer Res., 2013; Pantel et al., Nature Med. 2013; Heitzer et al., Genome Med. 2013; Schwarzenbach et al., Nature Rev. Clin. Oncol., 2014). This information can be used as companion diagnostics to improve the stratification of therapies and to obtain insights into therapy-induced selection of cancer cells (Wan, Pantel, Kang, Nature Med. 2013).