LAUSR

Simple Summary Gastrointestinal cancers have a high mortality rate worldwide, and the progression of the disease is related to cancer stem cells. Until now, its relationship with the microenvironment has been poorly understood. We describe the molecules and different pathways activated during this interaction and the new targeting therapies for cancer cells and microenvironment modulation. This approach could impact the way gastrointestinal cancers are managed. Abstract Gastrointestinal adenocarcinomas are one of the world’s deadliest cancers. Cancer stem cells and the tissue microenvironment are highly regulated by cell and molecular mechanisms. Cancer stem cells are essential for maintenance and progression and are associated with resistance to conventional treatments. This article reviews the current knowledge of the role of the microenvironment during the primary establishment of gastrointestinal adenocarcinomas in the stomach, colon, and rectum and its relationship with cancer stem cells. We also describe novel developments in cancer therapeutics, such as targeted therapy, and discuss the advantages and disadvantages of different treatments for improving gastrointestinal cancer prognosis.