Immune regulation in gastric adenocarcinoma is linked with therapeutic efficacy and improved recovery

Abstract

Adenocarcinomas are one of the most common histological types of gastric cancer. It has been ranked fifth among common cancers and is the third among death causing cancers worldwide. The high mortality rate among patients with gastric cancer is because of its silent evolution, genetic heterogeneity, high resistance to chemotherapy as well as unavailability of highly effective therapeutic strategy. Until now a number of several treatment strategies have been developed and are being practiced such as surgery, chemotherapy, radio therapy, and immunotherapy, however, further developments are required to improve the treatment responses and reduce the side effects. Therefore, novel personal therapeutic strategies based on immunological responses should be developed by targeting different check points and key immune players. Targeting macrophages and related molecular elements can be useful to achieve these goals. In this minireview, we discuss the available treatment options, molecular underpinnings and immunological regulations associated with gastric adenocarcinoma. We further describe the possible check points and immunological targets that can be used to develop novel therapeutic options.

Keywords: adenocarcinomas; biomarker; diagnosis; gastric cancer; therapy.

FIGURE 1

This figure depicts some key features of gastric cancer subtypes based on molecular biology. Inset charts represent the distribution of molecular subtypes in gastric tumours obtained stomach. The molecular classification of gastric cancer indicates four prominent genomic subtypes (Genomically stable tumours, EBV-infected tumours; chromosomally unstable tumours, and Microsatellite instability (MSI) tumours. This figure was adopted from The Cancer Genome Atlas Research Network according to the rights and permissions statement of the publisher (Comprehensive molecular characterization of gastric adenocarcinoma., 2014). (CIN, chromosomal instability; EBV, Epstein-Barr virus; MSI, Microsatellite instability; GS, genomically stable).

FIGURE 2

This figure shows Want signaling pathway, and the associated regulatory mechanisms. Negative or positive feedback mechanisms associated with Wnt signaling pathway depend on the interaction between different molecules, which determine the function and importance of this pathway in gastric adenocarcinoma. In this pathway, Wnt ligand is facilitated to bind to FZD-LRP5/6 complex, while the destruction complex is inhibited by dishevelled (DVL), which prevents the degradation of β-catenin. β-catenin is accumulated in the cytoplasm followed by translocation into the nucleus, thereby activating transcription factors (Figure 2). The negative regulators of the Wnt signaling pathway are RNF43 and LRP1B (A). In case of mutation of loss of function of RNF43 or LRP1B, Wnt signaling is increased (B). The figure was adopted from the article published by Holm et al. (Holm et al., 2023) following the rights and permissions statement from the licensing agency/publisher. (DC; destruction complex, RNF; Ring Finger Protein, LRP; lipoprotein receptor-related protein, TCF; T-cell factor, LEF; lymphoid enhancer factor, LGR; Leucine-rich repeat-containing G-protein-coupled receptor, APC/MCC; Familial Adenomatous Polyposis).