Abstract
Gastrointestinal cancers are still responsible for high numbers of cancer-related deaths despite advances in therapy. Tumor-associated cells play a key role in tumor biology, by supporting or halting tumor development through the production of extracellular matrix, growth factors, cytokines, and extracellular vesicles. Here, we review the roles of these tumor-associated cells in the initiation, angiogenesis, immune modulation, and resistance to therapy of gastrointestinal cancers. We also discuss novel diagnostic and therapeutic strategies directed at tumor-associated cells and their potential benefits for the survival of these patients.
Highlights
Gastrointestinal (GI) cancers represent the most prevalent tumors worldwide and the major cause of death related to cancer
A recent study showed that exosomes derived from early- or late-stage CRC cell lines induce the activation of quiescent fibroblasts into distinct functional subtypes [59]
Lu et al showed that CRC stemness is induced through paracrine activation of Notch signaling, whereby membranebound Jagged-1 on Endothelial cells (ECs) is cleaved by ADAM metalloproteinase domain 17 (ADAM17), releasing a truncated soluble fragment that binds Notch on CRC cells
Summary
Gastrointestinal (GI) cancers represent the most prevalent tumors worldwide and the major cause of death related to cancer Within this group, we can identify colon, stomach, and liver cancers as the main concerns according to their prevalence (fourth, sixth, and seventh most prevalent, respectively). As a cause of death, stomach (second higher), liver (third higher), and colon cancer (fifth higher) are the main culprits [1] Colon and rectum cancers are usually diagnosed at early stages and are treated with surgery (colon cancer [3]), or multimodality treatment including chemoradiotherapy and surgery (rectum cancer [4]) with high rates of success, especially in the latter Other tumors such as PDAC are usually diagnosed at later stages, when surgery approaches are usually no longer feasible. We will focus on the role of these tumor-associated cells in the tumorigenesis and progression of GI cancers, as well as on their role in treatment resistance and potential targeted therapeutic approaches
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