Vol. 4, Issue 1, Part A (2024)

D44 isoform switching, a dynamic process involving the interchange between different CD44 variant isoforms, has emerged as a critical regulator of colorectal cancer phenotypic plasticity and therapeutic resistance. This review delves into the complex mechanisms underlying CD44 isoform switching, highlighting the role of transcriptional, post-transcriptional, and signaling pathway regulators in modulating the expression of CD44 standard and variant isoforms. The review further explores the link between CD44 isoform switching and the acquisition of distinct colorectal cancer cell phenotypes, such as increased migratory, invasive, and stem-like properties. Finally, this review discuss the therapeutic potential of targeting CD44 isoform switching to overcome the adaptive capabilities of colorectal tumor cells and improve patient outcomes.