Milk-Derived Proteins and Peptides as Natural Anticancer Agents: A Critical Narrative Review of Mechanisms, Evidence and Translational Readiness

Abstract

Milk proteins contain intact bioactive molecules and encrypted peptide sequences that can influence cell survival, redox regulation, immunity and tumour-associated signalling. Interest in their anticancer potential has expanded from early observations of tumour-selective cytotoxicity to defined lactoferrin-derived peptides, casein fragments, whey hydrolysates and alpha-lactalbumin-oleic acid complexes. This critical narrative review evaluates whether these entities can reasonably be regarded as natural anticancer agents and distinguishes mechanistic plausibility from evidence relevant to treatment or prevention. Literature published from 1995 to 15 June 2026 was selected through searches of multidisciplinary and biomedical scholarly sources, citation tracing and reference verification. The strongest mechanistic convergence concerns lactoferrin and lactoferricin, for which direct membrane effects, apoptosis, modulation of tumour metabolism, inhibition of angiogenic signalling and context-dependent immunomodulation have been demonstrated across several experimental systems. Alpha-lactalbumin-oleic acid complexes show reproducible cytotoxicity and limited human proof-of-concept, but the contribution of the milk protein remains disputed because oleic acid can account for much of the observed toxicity and non-malignant cells are not invariably spared. Casein-derived peptides and caseinate preparations show antileukaemic, antiproliferative and anti-invasive effects in selected models, yet contradictory prostate-cell findings and marked preparation dependence argue against a class-wide anticancer effect. Whey protein mixtures and hydrolysates provide signals in colorectal carcinogenesis models and support nutrition in patients with cancer, but clinical nutritional benefit should not be conflated with direct antitumour efficacy. Across candidate classes, translation is constrained by incomplete pharmacokinetics, gastrointestinal proteolysis, high experimental concentrations, inconsistent normal-cell controls, heterogeneous processing and sparse cancer-specific trials. Milk-derived proteins and peptides therefore constitute a credible discovery platform rather than an established therapeutic class; the most defensible path forward is chemically defined, mechanism-linked development with rigorous selectivity, exposure and clinical validation.