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.
Highlights
The term liquid biopsy simultaneously encompasses a group of significantly different techniques, emerging as a tool that clinical practitioners can use to diagnose cancer, assess prognosis, identify targetable alterations, predict the effectiveness of treatments, and monitor tumor burden and therapeutic resistance
While no correlation was found between circulating tumor DNA (ctDNA) positivity preoperatively and cancer recurrence, the detection of ctDNA postoperatively was significantly associated with cancer recurrence in the first year (p = 0.029), and the median time observed between ctDNA detection and radiologic cancer recurrence was 4.05 months [49]
The authors showed a consistent correlation of clonal mutations between tumor and peripheral blood samples, identifying 32 mutations potentially related to trastuzumab resistance, and defined another valuable biomarker to monitor response to chemotherapy, the molecular Tumor Burden Index, as an independent prognostic factor for progression-free survival [89]
Summary
The term liquid biopsy simultaneously encompasses a group of significantly different techniques, emerging as a tool that clinical practitioners can use to diagnose cancer, assess prognosis, identify targetable alterations, predict the effectiveness of treatments, and monitor tumor burden and therapeutic resistance. The potential for liquid biopsy has been most thoroughly studied in colorectal cancer, non-small cell lung cancer, and breast cancer and less explored in gastric cancer [1,2,3]. In our introduction, following a brief description of gastric cancer’s prognostic and predictive biomarkers, we provide a brief overview of the history and applications of liquid biopsy. It is not the purpose of this article to describe the technical and procedural background and limitations of liquid biopsy, which would go beyond the scope of this review. Readers may refer to some of the excellent recent reviews on this topic [1,2,3]
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