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Manuscript Submission Deadline 14 March 2024

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Gastrointestinal (GI) cancers represent the most prevalent tumors worldwide and the leading cause of cancer-related death. In 2020, they accounted for an estimated 3.5 million global deaths, with an additional 5.0 million new cases diagnosed in the same year. Accumulated evidences in recent years has clearly demonstrated that tumor growth and resistance to therapy are influenced by the tumor microenvironment (TME), which consists in both cellular (i.e. cancer stem cells, immune cells, tumor-associated macrophages, cancer-associated fibroblast, blood and lymphatic vessels) and non-cellular components (i.e. collagen, proteoglycans, laminins and other extracellular matrix components). The cross-talk between TME cells is influenced by a complex and dynamic network of cytokines, chemokines, growth factors. Strategies aimed at targeting this communication have been explored, but results have been limited and debated.

The high heterogeneity and complexity of TME in gastrointestinal cancers has been a challenge for the development of effective anti-cancer therapies. One crucial factor associated with chemoresistance is the presence of a distinct population of cancer stem cells (CSCs). These CSCs possess the ability to self-renew and replicate the entire tumor heterogeneity, making them responsible for metastasis spreading and recurrence. Furthermore, CSCs displays unique metabolic features, which enable them to adapt to different physiological conditions, such as hypoxia, pH of the microenvironment, etc. Additionally, CSCs tend to be predominantly quiescent, rendering them highly resistant to chemotherapy, which is the gold standard treatment for GI cancers. Therefore, exploring novel strategies to target this subpopulation could have an impact on the composition of the tumor microenvironment, as well as tumor progression.

This Special Issue was set up to encourage researchers to carry out studies on:
- Heterogeneity in Gastrointestinal (GI) cancers;
- Crosstalk between tumors and stromal environment;
- Targeting tumor metabolism;
- Cancer Stem Cells (CSCs) and their role in therapies failure;
- CSCs metabolism;
- Novel strategies or targeting GI cancers progression.

Keywords: gastrointestinal cancers, tumor microenvironment, metabolism in cancer, cancer stem cells, targeted therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Gastrointestinal (GI) cancers represent the most prevalent tumors worldwide and the leading cause of cancer-related death. In 2020, they accounted for an estimated 3.5 million global deaths, with an additional 5.0 million new cases diagnosed in the same year. Accumulated evidences in recent years has clearly demonstrated that tumor growth and resistance to therapy are influenced by the tumor microenvironment (TME), which consists in both cellular (i.e. cancer stem cells, immune cells, tumor-associated macrophages, cancer-associated fibroblast, blood and lymphatic vessels) and non-cellular components (i.e. collagen, proteoglycans, laminins and other extracellular matrix components). The cross-talk between TME cells is influenced by a complex and dynamic network of cytokines, chemokines, growth factors. Strategies aimed at targeting this communication have been explored, but results have been limited and debated.

The high heterogeneity and complexity of TME in gastrointestinal cancers has been a challenge for the development of effective anti-cancer therapies. One crucial factor associated with chemoresistance is the presence of a distinct population of cancer stem cells (CSCs). These CSCs possess the ability to self-renew and replicate the entire tumor heterogeneity, making them responsible for metastasis spreading and recurrence. Furthermore, CSCs displays unique metabolic features, which enable them to adapt to different physiological conditions, such as hypoxia, pH of the microenvironment, etc. Additionally, CSCs tend to be predominantly quiescent, rendering them highly resistant to chemotherapy, which is the gold standard treatment for GI cancers. Therefore, exploring novel strategies to target this subpopulation could have an impact on the composition of the tumor microenvironment, as well as tumor progression.

This Special Issue was set up to encourage researchers to carry out studies on:
- Heterogeneity in Gastrointestinal (GI) cancers;
- Crosstalk between tumors and stromal environment;
- Targeting tumor metabolism;
- Cancer Stem Cells (CSCs) and their role in therapies failure;
- CSCs metabolism;
- Novel strategies or targeting GI cancers progression.

Keywords: gastrointestinal cancers, tumor microenvironment, metabolism in cancer, cancer stem cells, targeted therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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