Future perspectives of circulating tumor DNA in colorectal cancer

Abstract

Tumor biopsy is currently the gold standard for diagnosis and in determining cell signaling pathways involved in the development of treatment resistance. However, there are major challenges with this technique, including the need for serial sampling to monitor treatment resistance, which is invasive and also has the potential for selection bias due to intra-tumoral and inter-tumoral heterogeneity. These challenges highlight the need for more effective methods for obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells shed into the blood from the primary tumor and metastatic sites and consequently provides a comprehensive, real-time picture of the tumor burden in an individual patient. Indeed, liquid biopsy has the potential to revolutionize cancer management. Here, we review recent studies on the potential clinical applications of liquid biopsy using circulating tumor DNA in colorectal cancer, including screening, diagnosis, detection of minimal residual disease after surgery, detection of recurrence, prognosis, predicting treatment response, monitoring tumor burden or response during treatment, and tracking resistance. We also discuss recent data demonstrating the utility of detecting KRAS-mutated circulating tumor DNA, both at diagnosis to determine an appropriate treatment strategy and during anti-epidermal growth factor receptor therapy to predict treatment resistance. The future integration of liquid biopsy into clinical practice is discussed, together with alternative approaches and key questions that need to be answered in future clinical studies before this technology can be implemented and used routinely.

The Developing Story of Predictive Biomarkers in Colorectal Cancer

“…An Alu-based quantitative-PCR could differentiate tumors from adenomas, based on evaluation of cfDNA levels [97]. Aberrant patterns of methylation have been described in the cfDNA [98]. The methylation status of the Septin 9 gene promoter has been used for the diagnosis of early CRC, and the reported sensitivity and specificity is 30–75%, and 90%, respectively [99].…”

Detection of KRAS mutations in liquid biopsies from metastatic colorectal cancer patients using droplet digital PCR, Idylla, and next generation sequencing

“…However, when the first response to treatment evaluation was performed, in one patient ddPCR values become zero with a clear increase of CEA and without a significant decrease in CA19-9 measurements, and in several patients the reduction in ddPCR values was more pronounced when compared to these classic serum tumor markers. These differences may at least partially depend on the short half-life of ctDNA in the blood when compared to the protein tumor markers [15].…”

Application and optimization of minimally invasive cell-free DNA techniques in oncogenomics

“…90 However, the desirability of using cfDNA as a biomarker lies in its non-invasive nature and accessibility, and a combined use with previously established tumor markers (Table 2) could be the first step toward the clinical approach to improve cancer diagnosis, treatment, and minimal residual disease monitoring. 117 Furthermore, technological advances via NGS have already revolutionized the field of cancer genomics by facilitating the detection of cancer-specific alterations in KRAS, EGFR, BRAF, and PIK3CA in plasma samples of lung, breast, and colorectal cancer patients as a new and developing area of research. 114 Although biomarker discovery is a budding field, several other tumor entities still lack frequent genetic changes, accentuating the necessity for the discovery of cancer-specific signatures in improving the analytical and diagnostic sensitivity of cancer.…”