Tehran University of Medical Sciences Acta Biochimica Iranica 0001-5261 3 1 2025 03 28 6 16 EN Elaheh Gheybi Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Pejman Hosseinzadeh Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Vahid Tayebi-Khorrami Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran Mehdi Rostami Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Mohammad Soukhtanloo Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 2025 05 27 2025 08 16 In the field of cancer biology, elucidating the factors that promote cancer cell invasion and progression is crucial for the identification of novel therapeutic targets. CD44 has emerged as a vital biomarker with significant implications for innovative treatment modalities, particularly in immunotherapy. This receptor is predominantly expressed on cancer stem cells, which play a pivotal role in tumorigenesis and contribute to therapeutic resistance. Elevated levels of CD44 are associated with aggressive cancer phenotypes, including enhanced metastatic potential and increased resistance to chemotherapy. Therefore, targeting CD44 may enhance the efficacy of cancer treatments. Notably, CD44 exists in multiple isoforms, each exhibiting unique expression patterns across different tissues and types of cancer, highlighting the need for a refined approach to clinical targeting. The variations among these isoforms can influence tumor behavior and treatment responses, underscoring the importance of understanding these distinctions for the optimization of therapeutic strategies. This review aims to delineate key aspects of breast cancer, emphasize the significance of the CD44 biomarker, and explore the implications of its isoforms in diagnosis and treatment. By scrutinizing these elements, we seek to clarify the role of CD44 in cancer biology and its potential for enhancing treatment approaches in breast cancer and other malignancies. https://abi.tums.ac.ir/index.php/abi/article/view/123 https://abi.tums.ac.ir/index.php/abi/article/download/123/96