The Emerging Role of Liquid Biopsy in Gastric Cancer

Abstract

(1) Background: Liquid biopsy (LB) is a novel diagnostic method with the potential of revolutionizing the prevention, diagnosis, and treatment of several solid tumors. The present paper aims to summarize the current knowledge and explore future possibilities of LB in the management of metastatic gastric cancer. (2) Methods: This narrative review examined the most recent literature on the use of LB-based techniques in metastatic gastric cancer and the current LB-related clinical trial landscape. (3) Results: In gastric cancer, the detection of circulating cancer cells (CTCs) has been recognized to have a prognostic role in all the disease stages. In the setting of localized disease, cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) qualitative and quantitative detection have the potential to inform on the risk of cancer recurrence and metastatic dissemination. In addition, gastric cancer-released exosomes may play an essential part in metastasis formation. In the metastatic setting, the levels of cfDNA show a positive correlation with tumor burden. There is evidence that circulating tumor microemboli (CTM) in the blood of metastatic patients is an independent prognostic factor for shorter overall survival. Gastric cancer-derived exosomal microRNAs or clonal mutations and copy number variations detectable in ctDNA may contribute resistance to chemotherapy or targeted therapies, respectively. There is conflicting and limited data on CTC-based PD-L1 verification and cfDNA-based Epstein–Barr virus detection to predict or monitor immunotherapy responses. (4) Conclusions: Although preliminary studies analyzing LBs in patients with advanced gastric cancer appear promising, more research is required to obtain better insights into the molecular mechanisms underlying resistance to systemic therapies. Moreover, validation and standardization of LB methods are crucial before introducing them in clinical practice. The feasibility of repeatable, minimally invasive sampling opens up the possibility of selecting or dynamically changing therapies based on prognostic risk or predictive biomarkers, such as resistance markers. Research is warranted to exploit a possible transforming area of cancer care.

Establishment of an Immune Cell Infiltration Score to Help Predict the Prognosis and Chemotherapy Responsiveness of Gastric Cancer Patients

“…The non-invasive concepts rendered liquid biopsy unparalleled charm and advantages. Its application value lies in tumor occurrence and progression monitoring, systemic therapy response prediction and early detection of metastatic disease (53). As a kind of circRNAs detectable in plasma, Hsa_circ_0000745 was involved in development processes of (GC) and may serve as promising diagnostic marker for GC in combination with CEA (54).…”

“…Published results showed that ctDNA levels in GI tumors were significantly higher compared to non-GI tumors. Interestingly, one-third of the alterations detected in tumors were detected only in ctDNA, not in the tissue sample (53,56). In a prospective trial that has enrolled 93 patients with resectable gastric cancer, patients with CTCs ≥ 5/7.5 mL detected in postoperative blood samples had significantly inferior disease-free survival (DFS) and overall survival (OS) than those with a smaller number of CTCs (57).…”

Exosomal RNAs in diagnosis and therapies

“…[ 67 ]). As an illustration, we review several key roles for cancer-related exosomes below; more comprehensive reviews of exosomes in various neoplastic diseases have been published recently [ [68] , [69] , [70] , [71] , [72] ].…”

Plasma-Based Genotyping in Advanced Solid Tumors: A Comprehensive Review

“…This article provides an overview of current and future applications of plasma ctDNA-based assays in select advanced solid malignancies, including recent guidelines and recommendations. The review focuses on breast, prostate, ovarian, lung, and colorectal malignancies, but the application of plasma-based testing extends to several other solid tumors and has been highlighted in recent comprehensive reviews [ 14 , 15 , 16 , 17 , 18 ]. In addition, the results of recent trials demonstrating the clinical utility of plasma ctDNA assays are interpreted in the context of current clinical practice and the evolving treatment landscape for solid tumors.…”