Liquid Biopsy for Prognosis and Treatment in Metastatic Colorectal Cancer: Circulating Tumor Cells vs Circulating Tumor DNA

Abstract

Liquid biopsy recently gained widespread attention as a noninvasive alternative/complementary technique to tissue biopsy in patients with cancer. As technological advances have improved both feasibility and turnaround time, liquid biopsy has expanded tumor molecular analysis with acknowledgement of both spatial and temporal heterogeneity, overcoming many limitations of traditional tissue biopsy. Because of its diagnostic, prognostic, and predictive value, liquid biopsy has been extensively studied also in metastatic colorectal cancer. Indeed, as personalized medicine establishes its role in cancer treatment, genetic biomarkers unveiling the emergence of early resistance are needed. Among the wide variety of tumor analytes amenable to collection, circulating DNA and circulating tumor cells are the most adopted approaches, and both carry clinical relevance in colorectal cancer. However, few studies focused on comparing feasibility between these two approaches. In this review, we discuss the potential implications of liquid biopsy in metastatic colorectal cancer, assessing the advantages and drawbacks of circulating DNA and circulating tumor cells, and highlighting the most relevant trials for clinical practice.

Clinical Impact of Primary Tumor Location in Metastatic Colorectal Cancer Patients Under Later-Line Regorafenib or Trifluridine/Tipiracil Treatment

“…( 11 , 12 ) High thymidine kinase 1 (TK1) expression level correlated with a larger survival benefit in FTD/TPI treatment, ( 30 ) although no significant difference in TKI expression according to PTL was reported. Moreover, evolving technologies of liquid biopsies using circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) analysis have accelerated research on the dynamism of clonal evolution, enabling us to reveal molecular profiling, monitor clonal dynamics, and identify resistance mechanism by longitudinal biopsies ( 31 – 33 ). The subgroup and exploratory biomarker analyses in the CORRECT trial suggested that a survival benefit was observed regardless of RAS or PIK3CA mutational status in ctDNA.…”

Clinical management of metastatic colorectal cancer in the era of precision medicine

“…59 Furthermore, assessment of ctDNA allows the comprehensive detection of different mutated cancer clones, which may arise in different metastatic sites. 60 In this respect, several NGS extended gene panels for liquid biopsy analysis are currently available.…”

“…A potential advantage of liquid biopsy is the possibility of repeating this procedure to evaluate the dynamic tumor mutation changes under the selective pressure of therapies for a better choice of molecular target drugs to use 59 . Furthermore, assessment of ctDNA allows the comprehensive detection of different mutated cancer clones, which may arise in different metastatic sites 60 . In this respect, several NGS extended gene panels for liquid biopsy analysis are currently available.…”

Clinical Characteristics of Metastatic Colorectal Cancer Combined with Gastrointestinal Perforation and Prognostic Value of Circulating Tumor DNA

“…Circulating tumor DNA (ctDNA) is a small fragment of gene released from solid lesions into the circulation system, mainly derived from tumor metabolism, and the genomic information carried by it is highly consistent with tumor tissue [ 3 ]. Relevant studies have pointed out that ctDNA detection can more accurately reflect the epigenetics of tumor-related genes, and then can be used to track the occurrence and development of tumors in the body [ 4 ]. At present, many clinical studies [ 5 , 6 ] have shown that it can be used in the prognostic evaluation of various tumors.…”