Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy

Abstract

Response evaluation for cancer treatment consists primarily of clinical and radiological assessments. In addition, a limited number of serum biomarkers that assess treatment response are available for a small subset of malignancies. Through recent technological innovations, new methods for measuring tumor burden and treatment response are becoming available. By utilization of highly sensitive techniques, tumor-specific mutations in circulating DNA can be detected and circulating tumor DNA (ctDNA) can be quantified. These so-called liquid biopsies provide both molecular information about the genomic composition of the tumor and opportunities to evaluate tumor response during therapy. Quantification of tumor-specific mutations in plasma correlates well with tumor burden. Moreover, with liquid biopsies, it is also possible to detect mutations causing secondary resistance during treatment. This review focuses on the clinical utility of ctDNA as a response and follow-up marker in patients with non-small cell lung cancer, melanoma, colorectal cancer, and breast cancer. Relevant studies were retrieved from a literature search using PubMed database. An overview of the available literature is provided and the relevance of ctDNA as a response marker in anti-cancer therapy for clinical practice is discussed. We conclude that the use of plasma-derived ctDNA is a promising tool for treatment decision-making based on predictive testing, detection of resistance mechanisms, and monitoring tumor response. Necessary steps for translation to daily practice and future perspectives are discussed.

Early, On-Treatment Levels and Dynamic Changes of Genomic Instability in Circulating Tumor DNA Predict Response to Treatment and Outcome in Metastatic Breast Cancer Patients

“…In the metastatic setting, monitoring patients with ctDNA and identifying patients who progress during treatment earlier than with imaging techniques could provide the opportunity to prompt clinical intervention to modify the patient’s line of treatment [ 28 ]. However, prospective clinical trials are still needed to determine if early treatment modifications based on ctDNA changes can improve the clinical outcome [ 29 , 30 ]. Interestingly, of five patients presenting the pattern of nonresponse (#2), two presented very aggressive diseases and died within one month of treatment, and for two other patients, additional blood samples were analyzed, and we observed a continuous increase in GIN over time until the time of progression and patient’s death ( Figure S9 ).…”

Circulating Tumour DNA in Advanced Melanoma Patients Ceasing PD1 Inhibition in the Absence of Disease Progression

“…Circulating tumour DNA (ctDNA), released into plasma from apoptosing or necrotic tumour cells, has emerged as a useful biomarker for assessment of response to therapy in various cancers [ 8 , 9 , 10 ]. In melanoma, we and others have shown the clinical validity of using ctDNA for tracking response to therapy and prognostication [ 11 , 12 , 13 , 14 , 15 ].…”

Accurate detection of circulating tumor DNA using nanopore consensus sequencing

“…Circular DNA obtained by the circularization reaction was combined with 12 μl 5X Annealing buffer (50 mM Tris @ pH 7.5-8.0, 250 mM NaCl, 5 mM EDTA) and 1 μl Exo-resistant random primers (Thermofisher), heated for 5 minutes at 98°C and then cooled down at room temperature. Subsequently, the RCA mix (previous reaction mixture, 10…”

“…Moreover, tumor locations (primary tumors or metastases) are not always easily accessible for taking biopsies and complications can occur. In this context, it has been shown that ctDNA detection in blood and other fluids ("liquid biopsies") is complementary to solid biopsies for detection of targets for precision medicine 10 .…”