Emerging Role of Circulating Tumor Cells in Gastric Cancer

Abstract

With over 1 million incidence cases and more than 780,000 deaths in 2018, gastric cancer (GC) was ranked as the 5th most common cancer and the 3rd leading cause of cancer deaths worldwide. Though several biomarkers, including carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), and cancer antigen 72-4 (CA72-4), have been identified, their diagnostic accuracies were modest. Circulating tumor cells (CTCs), cells derived from tumors and present in body fluids, have recently emerged as promising biomarkers, diagnostically and prognostically, of cancers, including GC. In this review, we present the landscape of CTCs from migration, to the presence in circulation, biologic properties, and morphologic heterogeneities. We evaluated clinical implications of CTCs in GC patients, including diagnosis, prognosis, and therapeutic management, as well as their application in immunotherapy. On the one hand, major challenges in using CTCs in GC were analyzed, from the differences of cut-off values of CTC positivity, to techniques used for sampling, storage conditions, and CTC molecular markers, as well as the unavailability of relevant enrichment and detection techniques. On the other hand, we discussed future perspectives of using CTCs in GC management and research, including the use of circulating tumor microembolies; of CTC checkpoint blockade in immunotherapy; and of organoid models. Despite the fact that there are remaining challenges in techniques, CTCs have potential as novel biomarkers and/or a non-invasive method for diagnostics, prognostics, and treatment monitoring of GC, particularly in the era of precision medicine.

Cut-Off Analysis of CTC Change under Systemic Therapy for Defining Early Therapy Response in Metastatic Breast Cancer

“…In a combined study for metastatic breast and prostate cancer, Coumans et al demonstrated that for initially CTC-positive patients, a decrease of CTC count below the cut-off after 6-8 weeks of therapy is the best indicator of treatment response [38]. The association of therapy response and conversion from positive to negative CTC status was also demonstrated for metastatic non-small cell lung cancer, locally advanced head and neck cancer and gastric cancer [39][40][41]. Lorente et al described a 30% CTC decline 4 weeks after treatment for castration-resistant prostate cancer with initially ≥5 CTCs/7.5 mL as independently associated with OS and a more sensitive biomarker than 50% CTC decline [27].…”

Neutrophil-Lymphocyte Ratio and Circulating Tumor Cells Counts Predict Prognosis in Gastrointestinal Cancer Patients

“…Thirdly, we only collected the peripheral blood and CTCs counts before chemotherapy or other therapy and we did not evaluate NLR and/or CTCs before and after chemotherapy or other therapy dynamically. Additionally, although CTCs had a different application for tumor prognosis, it is still difficult for CTCs to become common in the clinical practice because at present, the majority of CTCs detection is through epithelial markers (such as EpCAM and cytokeratins) and epithelial cell surface-associated glycoproteins (such as MUC-1) ( 1 ), whereas nowadays these methods tend to ignore CTCs with mesenchymal phenotypes. However, epithelial–mesenchymal transition can appear in the metastatic process of tumor, which means CTCs detection with mesenchymal markers may be more accurate ( 1 ).…”

“…GC and CRC are the most common malignancies in the world. The 5-year survival rate was approximately 30% in GC patients with radical surgery ( 1 ) and about 68.9% in CRC postoperative patients ( 2 ). The prognosis of GC and CRC patients was significantly correlated with tumor location, TNM stage, and the tumor size ( 3 ).…”

Ivermectin, a potential anticancer drug derived from an antiparasitic drug

“…Gastric cancer is one of the most common malignant tumors worldwide. In the past year, more than one million patients with gastric cancer have been diagnosed worldwide [ 38 ]. Nambara’s study showed that IVM could significantly inhibit the proliferation of gastric cancer cells in vivo and in vitro and that the inhibitory effect of IVM depended on the expression of Yes-associated protein 1(YAP1)[ 39 ].…”