scholarly journals Circulating Tumor DNA in Oncology

Processes ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 2198
Author(s):  
Saeko Sakaeda ◽  
Yoichi Naito

When somatic cells in the human body undergo apoptosis or necrosis, the released DNA enters the bloodstream. This type of DNA is called cell-free DNA (cfDNA). In patients with cancer, DNA released from tumor cells is called circulating tumor DNA (ctDNA), which carries genetic alterations specific to tumor cells. In recent years, ctDNA has attracted particular attention in terms of the concept of liquid biopsy in cancer care. Conventionally, tissue biopsy is required for the definitive diagnosis of cancer, and imaging examinations, such as CT, are performed for evaluating recurrence and residual lesions. Although the treatment burden on cancer patients is being slightly reduced due to advances in medicine, invasive examinations and medical exposure are still unavoidable. In addition, the prognosis of cancer varies considerably depending on the degree of progression at the time of detection. Therefore, the early detection of cancer is of utmost importance. With the increase in health consciousness, more people undergo regular health checkups, and it becomes necessary to diagnose cancer in a larger number of patients at an earlier stage. Although the accuracy of early detection has been improved by new imaging tests and examination techniques, each organ must be examined separately, and some organs are more difficult to examine than others in a regular health checkup. The process of cancer screening, diagnosis, and detection of recurrence after treatment is extensive. It can also be expensive, and some of the examinations may be invasive. If all of these processes can be replaced by the analysis of ctDNA in liquid biopsy, only a single blood sample is required. Under these circumstances, various studies are currently in progress on the use of ctDNA in clinical practice as an approach that may greatly reduce such burden. We present an overview of the current situation of ctDNA, as well as its future issues and prospects.

The Analyst ◽  
2020 ◽  
Vol 145 (16) ◽  
pp. 5553-5562
Author(s):  
Jiawei Wang ◽  
Guanping Hua ◽  
Lihuang Li ◽  
Danyang Li ◽  
Fanfan Wang ◽  
...  

A rapid molecular diagnostic technique targeting circulating tumor DNA (ctDNA) has become one of the most clinically significant liquid biopsy methods for non-invasive and timely diagnosis of cancer.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12502-e12502
Author(s):  
Wang Xiao Jia ◽  
Zhan-Hong Chen ◽  
Tian Sun ◽  
Zi Yan Yang ◽  
Yabing Zheng ◽  
...  

e12502 Background: Circulating tumor DNA (ctDNA) from liquid biopsy provides a valuable assessment of invasive breast cancer (BC). We evaluated the utility of ctDNA to reflect the efficacy of HER2-targeted trastuzumab in treating HER2+ BC patients, as well as chemotherapy in treating HER2- BC patients, to monitor trastuzumab and chemotherapy resistance mechanisms. Methods: Targeted next-generation sequencing (NGS) of 416 cancer-relevant genes was performed in 41 plasma biopsy samples from 19 HER2+ and 12 HER2- BC patients in a retrospective study. We compared ctDNA somatic mutations and germline mutations for analyzing acquired and innate resistance, respectively. Results: ERBB2 somatic copy number of HER2+ BC patients who developed progressed diseases to HER2-target therapy was significantly higher than those benefited from HER2-target therapy. HER2+ BC patients who developed acquired resistance to trastuzumab showed frequent genomic alterations on ERBB2, TP53, EGFR, NF1 and SETD2 genes. Specifically, in longitudinal analyses, somatic mutations found in the original breast tumor can be detected in the liver metastasis and plasma ctDNA with increased allele frequencies. Newly emerged deleterious mutations occurred when the patient was benefiting from trastuzumab, predicting the poor prognosis. From these newly emerged somatic mutations, EBBB2L869R was further investigated in vitro and contributed to trastuzumab resistance. In the HER2- BC patients with chemotherapy resistance, frequently genetic alterations on TP53, PIK3CA and DNA damage repair genes were observed in ctDNA mutation profiling. Conclusions: liquid biopsy ctDNA, particularly longitudinal analyses, provides insights into targeted therapy efficacy and gene alterations underlying trastuzumab resistance and chemotherapy resistance in HER2+ and HER2- BC patients, respectively.


2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Fiona Tsui-Fen Cheng ◽  
Nina Lapke ◽  
Chin-Chu Wu ◽  
Yen-Jung Lu ◽  
Shu-Jen Chen ◽  
...  

Genetic alterations in circulating tumor DNA (ctDNA) are an emerging biomarker for the early detection of relapse and have the potential to guide targeted treatment. ctDNA analysis is often performed by droplet digital PCR; however, next-generation sequencing (NGS) allows multigene testing without having to access a tumor sample to identify target alterations. Here, we report the case of a stage III hormone receptor-positive breast cancer patient who remained symptomless after receiving surgery and adjuvant chemotherapy. Liquid biopsy analysis by NGS revealed the presence of a ctDNA PIK3CA N345K mutation five months before the detection of relapse with multiple liver metastases by regular clinical follow-up. To date, clinical implications of the PIK3CA N345K variant remain insufficiently investigated; however, everolimus treatment resulted in the shrinkage of tumor lesions and decreased the levels of tumor markers. Four months after treatment initiation, a second ctDNA analysis suggested a relapse, and the patient clinically progressed after five months of everolimus therapy. This case report demonstrates the value of ctDNA analysis by NGS for the early detection of relapse in breast cancer patients. The study further indicates its usefulness for the choice of targeted treatments, suggesting that the variant PIK3CA N345K might be associated with everolimus sensitivity.


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