CD44: A New Prognostic Marker in Colorectal Cancer?

Simple Summary: CD44 is a crucial factor in colorectal cancer, with specific isoforms demonstrating their significance in the development, progression, metastasis, and resistance to therapy. Given the clinical and pathological impact of CD44, it represents a promising molecular target for cancer therapy. In this review, we aim to highlight the predictive and prognostic significance of CD44 in various cancer types, with a particular focus on colorectal cancer. Moreover, we evaluate current therapeutic interventions that target CD44 or reduce its expression, thereby highlighting its potential as an effective therapeutic strategy. Cluster of differentiation 44 (CD44) is a non-kinase cell surface glycoprotein. It is overexpressed in several cell types, including cancer stem cells (CSCs). Cells overexpressing CD44 exhibit several CSC traits, such as self-renewal, epithelial–mesenchymal transition (EMT) capability, and resistance to chemo- and radiotherapy. The role of CD44 in maintaining stemness and the CSC function in tumor progression is accomplished by binding to its main ligand, hyaluronan (HA). The HA-CD44 complex activates several signaling pathways that lead to cell proliferation, adhesion, migration, and invasion. The CD44 gene regularly undergoes alternative splicing, resulting in the standard (CD44s) and variant (CD44v) isoforms. The different functional roles of CD44s and specific CD44v isoforms still need to be fully understood. The clinicopathological impact of CD44 and its isoforms in promoting tumorigenesis suggests that CD44 could be a molecular target for cancer therapy. Furthermore, the recent association observed between CD44 and KRAS-dependent carcinomas and the potential correlations between CD44 and tumor mutational burden (TMB) and microsatellite instability (MSI) open new research scenarios for developing new strategies in cancer treatment. This review summarises current research regarding the different CD44 isoform structures, their roles, and functions in supporting tumorigenesis and discusses its therapeutic implications. [ABSTRACT FROM AUTHOR]