Hepatic Metastasis in Gastrointestinal Cancers: Molecular Drivers, Microenvironmental Cues, and Therapeutic Horizons

Gastrointestinal (GI) tumor metastasis to the liver is one reason for the death of patients, and it has complicated development: the characteristics of tumor cells themselves and the liver microenvironment are both reprogrammed. In this review, we will look at the mechanism of the molecule and the cell of the liver metastasis of common GI malignant diseases such as gastric cancer, colorectal cancer, and pancreatic cancer. Firstly, from a tumor cell perspective, summarize the key intrinsic changes that drive metastasis, such as genetic mutations, epigenetic regulation (such as DNA methylation), the role of non-coding RNA (such as miRNA), the activation of the EMT program, and abnormal activation of certain transcription factors and CDKs. Second, the liver as a metastatic "target organ" along with the unique local surroundings for cancer metastasis—the extracellular matrix (e.g., TNF-α) and specific liver-resident cells (e.g.—hepatic sinusoidal endothelial cells)—are described and explained how those together cooperate through complex interaction with the free-flowing tumour cells during its circulation phase to form a local "premetastatic niche" that is permissive for tumour settlement. Finally, the paper talks about the present standard of care—it’s mainly surgical removal and systemic chemotherapy—and then checks out the opportunities and difficulties of new ways of treating cancer. These include targeted therapies like anti-VEGF drugs and immune checkpoint inhibitors. This paper stresses that in order to develop new methods for targeted prevention, diagnosis, and cure, it is necessary to have a multi-faceted and in-depth grasp of the mechanisms behind liver metastasis.