Liver metastasis of colorectal cancer: Mechanism and clinical therapy (Review)

Abstract

Liver metastasis is a common complication in colorectal cancer (CRC), with its presence and progression significantly shortening patient survival. Therefore, a deeper understanding of the underlying mechanisms driving liver metastasis in CRC is essential to identify more effective and actionable therapeutic targets and improve prognosis. Liver metastasis in CRC is a multifaceted and dynamic process. Tumor cells with invasive properties communicate with the surrounding microenvironment through mechanisms such as immune checkpoint molecules and cytokines, thereby establishing a supportive niche for their colonization and proliferation. Moreover, suppressive immune cells may enhance the invasiveness of tumor cells. The interplay between tumor cells and the microenvironment is an interdependent process. Targeting these interactions offers promising potential for novel therapeutic strategies. The present review outlined mechanisms of colorectal cancer liver metastasis, emphasizing the immune microenvironment's role, current treatment approaches, and future development prospects.

Keywords: colorectal cancer; immune microenvironment; liver metastasis; mechanism.

Figure 1.

Liver metastasis of colorectal cancer Acquisition of invasive phenotype of malignant cells is the driving force of colorectal liver metastasis. Tumor cells interact with immune cells in the microenvironment to reverse antitumor activity. The immune cells can be re-educated to promote progression and metastasis.

Figure 2.

Acquisition of invasive phenotype is regulated by numerous genes and signaling pathways of malignant cells in colorectal cancer. HGF, hepatocyte growth factor; RTK, receptor tyrosine kinase; TF, transcription factor; EMT, epithelial-mesenchymal transition; SMA, smooth muscle actin; FN, fibronectin; TIMP, tissue inhibitor of metalloproteinases; uPAR, urokinase-type plasminogen activator receptor; ZO-1, zonula occludens-1; MET, mesenchymal-epithelial transition.

Figure 3.

Interactions between tumor cells and microenvironmental immune cells contribute to the enhancement of tumor cell invasiveness. NK, natural killer; Th, helper T cell; DC, dendritic cell; Treg, regulatory T cell; MDSC, myeloid-derived suppressor cells.