β-Casomorphins as opioid peptide modulators of tumor biology and immune signaling

β-casomorphins (BCMs) are bioactive peptides generated from milk β-casein digestion, which interact with opioid and other receptors to affect both tumor cell proliferation and immune responses within the tumor microenvironment. This review is aimed at summarizing current evidence on the anti-proliferative and immunomodulatory activities of BCMs, in particular BCM-5 and BCM-7, and their relevance to cancer biology. Studies have shown that BCM-5 primarily inhibits cancer cell growth, whereas BCM-7, in addition, enhances anti-tumor immunity by promoting CD8⁺ T cell infiltration and reducing regulatory T cell populations. The review also discusses synthetic cyclic analogs designed to improve peptide stability and bioavailability, which demonstrate opioid-independent antiproliferative activities. By integration of mechanistic, in vitro, and in vivo data, this review emphasizes the potential of β-casomorphins and their derivatives as modulators of tumor progression and immune surveillance and identifies gaps in knowledge to guide future research in oncology.