Clinical Relevance of Mesenchymal- and Stem-Associated Phenotypes in Circulating Tumor Cells Isolated from Lung Cancer Patients

SIMPLE SUMMARY: Lung cancer is the most frequent malignancy in the world. Most lung cancer patients are diagnosed at an advanced stage. To make matters worse, the survival of patients is very poor. Circulating tumor cells (CTCs), albeit rare, have been portrayed as essential players in the progression of lung cancer. It is definitely not easy being a CTC. First, they escape from the primary tumor, then they travel in the bloodstream, have to survive really harsh conditions, and finally, they form metastases. The adoption of epithelial-to-mesenchymal transition as well as cancer stem cell features has been suggested to allow CTCs to survive and metastasize. This review will focus on how these features can be used to estimate the prognosis of lung cancer patients. ABSTRACT: Lung cancer is the leading cause of cancer-related mortality globally. Among the types of lung cancer, non-small-cell lung cancer (NSCLC) is more common, while small-cell lung cancer (SCLC) is less frequent yet more aggressive. Circulating tumor cells (CTCs), albeit rare, have been portrayed as essential players in the progression of lung cancer. CTCs are considered to adopt an epithelial-to-mesenchymal transition (EMT) phenotype and characteristics of cancer stem cells (CSCs). This EMT (or partial) phenotype affords these cells the ability to escape from the primary tumor, travel into the bloodstream, and survive extremely adverse conditions, before colonizing distant foci. Acquisition of CSC features, such as self-renewal, differentiation, and migratory potential, further reflect CTCs’ invasive potential. CSCs have been identified in lung cancer, and expression of EMT markers has previously been correlated with poor clinical outcomes. Thus far, a vast majority of studies have concentrated on CTC detection and enumeration as a prognostic tools of patients’ survival or for monitoring treatment efficacy. In this review, we highlight EMT and CSC markers in CTCs and focus on the clinical significance of these phenotypes in the progression of both non-small- and small-cell lung cancer.