Objective This study aimed to critically review the current evidence on the anticancer potential of the cell-derived secretome, with emphasis on mesenchymal stem/stromal cell (MSC) products, and to provide a realistic translational roadmap. Methods This narrative review analyzes preclinical studies ( in vitro ) published from 2000 until September 30, 2025, identified through PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. We focused on the secretome composition, its source-dependent variability, the reported antitumor mechanisms, and the factors responsible for the conflicting pro- versus anti-tumorigenic outcomes. This narrative review covers the literature from January 2000 up to December 1, 2025 (final search: PubMed/MEDLINE, Scopus, Web of Science, ClinicalTrials.gov; terms: “secretome” OR “exosome” AND “cancer” AND “clinical trial”). Key findings Numerous preclinical studies demonstrate that certain MSC-derived secretomes—particularly inflammatory-primed, serum-free preparations from perinatal tissues (Wharton’s jelly or umbilical cord) and extracellular vesicle (EV)-depleted or genetically/drug-loaded variants—consistently reduce the cancer cell viability, migration, angiogenesis, and tumor growth (55%–85% inhibition in rodent models) across breast, prostate, lung, glioma, and melanoma models. Conversely, unprimed adult tissue MSC secretomes and intact exosome fractions frequently exert neutral or tumor-promoting effects. Engineered platforms (e.g., TRAIL- or azurin-expressing MSCs and paclitaxel-primed amniotic cells) achieve the largest potency gains (from 10- to 100-fold) and favorable safety profiles in vivo . To date, no clinical trial has reported on the anticancer efficacy of any cell-free secretome product in humans. Translational implications Clinical advancement requires immediate consensus on an optimal perinatal-sourced candidate, mandatory priming/EV depletion, validated quantitative potency assays, and Good Manufacturing Practice (GMP)-compliant manufacturing. With coordinated effort, first-in-human phase I trials could commence by 2028–2029, offering a novel, off-the-shelf paracrine therapy for solid tumors.
Alrushaid et al. (Wed,) studied this question.