Research Progress for the Clinical Application of Circulating Tumor Cells in Prostate Cancer Diagnosis and Treatment

Abstract

Prostate cancer is a life-threatening and highly heterogeneous malignancy. In the past decade, circulating tumor cells (CTCs) have been suggested to play a critical role in the occurrence and progression of prostate cancer. In particular, as the “seed” of the cancer metastasis cascade, CTCs determine numerous biological behaviors, such as tumor invasion into adjacent tissues and migration to distant organs. Many studies have shown that CTCs are necessary in the processes of tumor progression, including tumorigenesis, invasion, metastasis, and colonization. Furthermore, CTCs express various biomarkers relevant to prostate cancer and thus can be applied clinically in noninvasive tests. Moreover, CTCs can serve as potential prognostic targets in prostate cancer due to their roles in regulating many processes associated with cancer metastasis. In this review, we discuss the isolation and detection of CTCs as predictive markers of prostate cancer, and we discuss their clinical application in the diagnosis and prognosis of prostate cancer and in monitoring the response to treatment and the prediction of metastasis.

Molecular Characterization of Prostate Cancers in the Precision Medicine Era

“…The main features of CTCs are rarity and heterogeneity: This is why separation and enrichment are challenging and represent the main limitation of this approach [ 147 ]. There are several sorting protocols that exploit different features of CTCs, such as volume, density and biomarkers.…”

“…For example, the CellSearch ® is an IVD-certified method in US for separation and counting of CTCs and it is based on the detection of epithelial cell adhesion molecule (EpCAM). Unfortunately, since CTCs are heterogeneous and undergo epithelial to mesenchymal transition (EMT) to escape the primary tumor, losing EpCAM and/or cytokeratin expression, this approach is not always ideal to succeed [ 146 , 147 ]. There are other commercially available platforms for CTCs isolation based on different technologies but despite the advantages of each one, there are also many drawbacks, including low cell viability or moderate sensitivity and doubts about accuracy in capturing viable CTCs [ 148 ].…”

“…Nevertheless, many studies have investigated the role of CTCs in PCa with respect to clinical utility. The number of CTCs has been correlated to therapeutic response and survival in metastatic PCa: Patients with shorter progression-free survival and overall survival have been shown to have higher CTC counts [ 146 , 147 , 149 ]. In addition, genomic analyses have been recently performed on CTCs, highlighting that CTCs derived from aggressive PCa show a high number of variants (single nucleotide variants and insertion/deletions) [ 147 ].…”

“…The number of CTCs has been correlated to therapeutic response and survival in metastatic PCa: Patients with shorter progression-free survival and overall survival have been shown to have higher CTC counts [ 146 , 147 , 149 ]. In addition, genomic analyses have been recently performed on CTCs, highlighting that CTCs derived from aggressive PCa show a high number of variants (single nucleotide variants and insertion/deletions) [ 147 ]. Genomic instability in CTCs has been correlated with aggressiveness in PCa, allowing to discriminate among metastatic PCa those cases prospectively stratified as resistant to therapy and with poor prognosis [ 149 ].…”

High CTC-TRPC5 Expression Significantly Associated With Poor Prognosis in Radical Resected Colorectal Cancer Patients

“…Circulating tumor cells (CTC) are tumor cells that are separated from solid tumor lesions which enter the blood circulatory system, where they can be detected in peripheral blood ( Smit et al, 2021 ). There are currently various technologies available that can separate CTC from blood using biophysical methods (deformability, size, density, and surface charge) and/or immunoaffinity status ( Khetani et al, 2018 ; Habli et al, 2020 ; Yang et al, 2021 ). Previous studies have found that the number of CTC in the peripheral blood of patients with CRC after surgery is significantly related to the prognosis ( Rahbari et al, 2010 ; Iinuma et al, 2011 ; Bork et al, 2015 ).…”