scholarly journals Molecular Evolutionary Process of Advanced Gastric Cancer During Sequential Chemotherapy Detected by Circulating Tumor DNA

2021 ◽  
Author(s):  
Wenqi Xi ◽  
Chenfei Zhou ◽  
Shouwei Zhang ◽  
Yi Zhao ◽  
Yawei Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Copy Number ◽  
Treatment Strategies ◽  
Evolutionary Process ◽  
Treatment Resistance ◽  
Circulating Tumor Dna ◽  
Copy Number Variations ◽  
Current Data ◽  
Sequential Chemotherapy

Abstract Background: Chemotherapy is the major strategy for advanced gastric cancer (AGC) patients, whereits efficacy has largely plateaued. Tumor evolutionary theory provides a promising strategy to optimize paradigm of cancer treatment, while current data of molecular changes during sequential chemotherapy is too insufficient to understandevolutionary process in tumors. Methods: Here, we performed NGS analysison 100 circulatingtumor DNA (ctDNA) samples collected from 27 AGC patients during treatment of sequentialchemotherapy. We observed dynamic changes of copy number instability (CNI) and gene-level copy number variations (CNVs) during the treatment.Results: Gene-levelCNV profiles were similar between baseline and end oftreatment. Subsequent regimens did not significantly change the CNV profiles driven by first-line regimens. Based on changes of copy number values of genes during treatment, resistance related genes of all four regimens were identified, respectively. These genes could be enriched into several common oncologic pathways, while exhibited a high inter-patient heterogeneity. Genes with different copy number values between baseline and end of treatment could be the targets of by molecular matched therapy. Conclusions: Our study provides important information to understand molecular evolutionary process of AGS patients during sequential chemotherapy first and can help to optimize future treatment strategies.

scholarly journals Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Zuhua Chen ◽  
Cheng Zhang ◽  
Mengqi Zhang ◽  
Beifang Li ◽  
Yunyun Niu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Treatment ◽  
Advanced Gastric Cancer ◽  
Copy Number ◽  
Chromosomal Instability ◽  
Therapeutic Response ◽  
Circulating Tumor Dna ◽  
The Mean ◽  
Tumor Dna ◽  
Somatic Copy Number Alteration

Abstract Gastric cancer is characterized by chromosomal instability. In this study, we investigated chromosomal instability quantified by copy number instability (CNI) score of circulating tumor DNA (ctDNA) during the drug treatment in advanced gastric cancer (AGC). A total of 55 pretherapeutic plasmas from 55 AGC patients and 75 plasmas during drug treatment of 26 AGC patients were collected. Plasma ctDNA was extracted and assessed by whole-genome sequencing (WGS) for somatic copy number alteration (SCNA), and according to which we calculated the CNI scores. We next assessed the correlations between chromosomal instability and therapeutic response. The cutoff value of chromosomal instability was defined as the mean + SD of the CNI scores (56.60) in cfDNA of plasmas from 100 healthy people. For 55 enrolled cases, chromosomal instability was observed in 27 (49%) prior to drug treatment, whose response rate (59%, 16/27) was higher than in 28 patients with stable chromosomes (32%, 9/28, P = 0.043). We also observed that CNI scores fluctuated during treatment in 26 patients. Specifically, the CNI scores in 93% (14/15) of patients sensitive to drug treatment reduced to the level of chromosomal stability and the CNI scores in 52% (13/25) of patients resistant to treatment elevated again. For ctDNA with developed resistance, the SCNA patterns were identical to those before treatment, whereas the CNI scores were lower than the pretherapeutic scores. We found that chromosomal instability based on ctDNA could predict and monitor therapeutic response in gastric cancer, although validation in a larger cohort will be necessary.

scholarly journals ADAR expression and copy number variation in patients with advanced gastric cancer

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Javad Behroozi ◽  
Shirin Shahbazi ◽  
Mohammad Reza Bakhtiarizadeh ◽  
Habibollah Mahmoodzadeh
Keyword(s):  
Gastric Cancer ◽  
Copy Number Variation ◽  
Advanced Gastric Cancer ◽  
Copy Number ◽  
Number Variation

scholarly journals Monitoring the HER2 copy number status in circulating tumor DNA by droplet digital PCR in patients with gastric cancer

2016 ◽  
Vol 20 (1) ◽  
pp. 126-135 ◽  
Author(s):  
Katsutoshi Shoda ◽  
Daisuke Ichikawa ◽  
Yuji Fujita ◽  
Kiyoshi Masuda ◽  
Hidekazu Hiramoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Copy Number ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Droplet Digital Pcr ◽  
Copy Number Status ◽  
Tumor Dna

scholarly journals Immunotherapy in Advanced Gastric Cancer: An Overview of the Emerging Strategies

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Helena Magalhães ◽  
Mário Fontes-Sousa ◽  
Manuela Machado
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Median Overall Survival ◽  
Systemic Disease ◽  
Treatment Strategies ◽  
Public Health Problem ◽  
Molecular Classification ◽  
Current Evidence ◽  
Curative Intent

Gastric cancer (GC) remains a public health problem, being the fifth most common cancer worldwide. In the western countries, the majority of patients present with advanced disease. Additionally, 65 to 75% of patients treated with curative intent will relapse and develop systemic disease. In metastatic disease, systemic treatment still represents the state of the art, with less than a year of median overall survival. The new molecular classification of GC was published in 2014, identifying four distinct major subtypes of gastric cancer, and has encouraged the investigation of new and more personalized treatment strategies. This paper will review the current evidence of immunotherapy in advanced gastric cancer.

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