Abstract
Globally, in 2018, 4.8 million new patients have a diagnosis of gastrointestinal (GI) cancers, while 3.4 million people died of such disorders. GI malignancies are tightly relevant to 26% of the world-wide cancer incidence and occupies 35% of all cancer-associated deaths. In this article, we principally investigated molecular and cellular mechanisms of tumorigenesis in five major GI cancers occurring at esophagus, stomach, liver, pancreas, and colorectal region that illustrate high morbidity in Eastern and Western countries. Moreover, through this investigation, we not only emphasize importance of the tumor microenvironment in development and treatment of malignant tumors but also identify significance of M2PK, miRNAs, ctDNAs, circRNAs, and CTCs in early detection of GI cancers, as well as systematically evaluate contribution of personalized precision medicine including cellular immunotherapy, new antigen and vaccine therapy, and oncolytic virotherapy in treatment of GI cancers.
Highlights
Gastrointestinal (GI) malignant tumors generally cover esophagus, stomach, liver, pancreas, as well as colorectal region
To support tumorigenesis and metastases, paracrinal and autocrinal transform growth factor b (TGFb) enhances immunosuppression through diminishing immune surveillance maintained by dendrite cells (DCs), cytotoxic T cells, and natural killer cells (NKs) cells as well as cytokines such as IL2 and INFg [22], amplifies angiogenesis through activation of ALK1 and ALK5 pathway and more production of vascular endothelial growth factor and connective tissue growth factors in epithelial cells and fibroblasts [97], and induces the epithelialmesenchymal transition (EMT) for promoting metastases through Smad-dependent and Smad-independent pathway [98], as well as accelerates malignant cells invasiveness through remodeling the extracellular matrix (ECM) and decreasing TbR2 signaling and miRNA-mediated protein regulation [99]
Due to high variability of single subclone- or multiple subclone-induced tumor evolution in the same tumor or metastatic regions of the same tumor, as well as in different types of GI cancers, intratumoral genomic heterogeneity is highly beneficial for early diagnosis via liquid biopsy [345,346,347], while intertumoral heterogeneity-mediated changes of temporal and spatial plasticity and stemness in the tumor microenvironment (TME) precisely support the significance of comprehensive therapeutic principle [348, 349]
Summary
Gastrointestinal (GI) malignant tumors generally cover esophagus, stomach, liver, pancreas, as well as colorectal region. Most primary cancers from those parts worldly covered 26% of cancer incidence and 35% of all deaths related to cancer, while 4.8 million new cases were yearly diagnosed and 3.4 million people lost their lives due to those malignancies, statistically in 2018 [1]. Tumorigenesis, Early Diagnosis, Cellular Immunotherapy combating with cancers over several centuries, many clinicians eventually and principally come back to the nature of malignant tumor, in which an outside exhibition of malignant tumors is uncontrolledly growing but the inside mechanism shows primary inhibition of immune surveillance and cytotoxic activity locally and systematically
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
