Nanoplatforms for Circulating Tumor Cell Detection in Lung Cancer.

Abstract

Analysis of circulating tumor cells (CTCs)2 and circulating tumor DNA, known as liquid biopsy, has received increasing attention because of its many potential clinical applications in the individual management of patients with cancer. Although CTC detection is currently more challenging than the analysis of circulating tumor DNA, one can obtain more information at the DNA, RNA, and protein levels from CTCs, and use CTCs for functional analyses. Thus, CTCs can also provide an important insight into tumor heterogeneity and enable investigation of biological mechanisms driving metastasis. Large-scale clinical studies have shown the accuracy of CTC counts as predictors of prognosis and response to therapy in different tumor entities (1). At present, there are >160 clinical trials for lung cancer alone listed on ClinicalTrials.gov, in which CTCs are used as investigative biomarkers. The availability of highly sensitive and flexible CTC analysis methods, particularly among patients with lung cancer, is of the highest clinical relevance. Further, approximately 70% of patients with non-small cell lung cancer (NSCLC) are diagnosed at stage III to IV, when a resection is no longer beneficial. Thus, only small biopsies are available from these patients, and these biopsies are not always sufficient to reflect the vast intratumoral heterogeneity of NSCLC; therefore, some druggable alterations may be overlooked. In the metastatic setting, if biopsies are collected, they are usually obtained from single sites and accordingly do not reflect the known tumor cell heterogeneity between different metastatic sites. CTCs are released from all sites and thus not only represent the cells with a high metastatic potential but also mirror the heterogeneity of the different tumor cells. Another benefit of CTC analyses compared with that of solid biopsy analyses is that blood analysis can be performed sequentially to monitor patients undergoing cancer therapy. However, the potential benefits of CTC analysis …