Malignant tumors of the digestive system are associated with high morbidity and mortality rates, and their incidence has been increasing among younger populations in recent years. Although current comprehensive treatment strategies, which are primarily based on surgical resection and integrated with neoadjuvant chemoradiotherapy, postoperative chemoradiation, targeted therapy, and immunotherapy, have achieved substantial progress, the prognosis for certain patients remains poor due to drug resistance, advanced disease stages, or poor treatment tolerance. Vanderbylia robiniophila, a traditional Chinese herbal medicine, has been utilized as both a first-line and adjunctive therapeutic agent for digestive system malignancies, and has demonstrated notable antitumor efficacy. In recent years, multiple in vitro studies have elucidated several underlying antitumor mechanisms, including modulation of tumor cell stemness, induction of tumor cell death, and regulation of the tumor microenvironment. This review summarized the current understanding of the molecular mechanisms through which Vanderbylia robiniophila exerts its antitumor effects, highlighting its considerable therapeutic potential in digestive system malignancies. In addition, it provided a comprehensive overview of the therapeutic efficacy and corresponding molecular mechanisms of Vanderbylia robiniophila across various digestive system cancers, thereby providing theoretical support for its clinical application. Furthermore, this review proposes future research directions to further elucidate the antitumor properties of Vanderbylia robiniophila, aiming to inform and inspire novel strategies for the comprehensive treatment of digestive system malignancies.
