J Transl Med. 2025 Dec 5. doi: 10.1186/s12967-025-07385-3. Online ahead of print.
ABSTRACT
INTRODUCTION: Inflammatory Bowel Disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is increasingly prevalent in China. Traditional treatments often have limited efficacy and safety, whereas molecular targeted therapies provide more precise and effective options with fewer adverse effects. The pathogenesis of IBD involves dysregulated inflammatory pathways including NF-κB, IL-23/Th17, and TGF-β. Major targeted therapies include TNF-α inhibitors, which are effective for induction and maintenance of remission (particularly when combined with immunomodulators), integrin antagonists, JAK inhibitors, limited IL-6 pathway inhibitors, and emerging agents targeting additional pathways. Biomarkers such as miR-21 and transcriptomic signatures support personalized treatment selection. Molecular targeted therapy has evolved from single-target strategies to multi-pathway modulation, improving clinical management. Nevertheless, challenges persist, including primary non-response, secondary loss of response, and safety risks. Further research is needed to refine sequencing strategies, integrate validated biomarkers into clinical practice, and optimize risk-benefit profiles.
BACKGROUND: The global burden of IBD continues to rise, particularly in newly industrialized regions such as China, where urbanization and lifestyle changes have accelerated incidence rates. Conventional therapies-aminosalicylates, corticosteroids, and traditional immunomodulators-often fail to sustain long-term remission in moderate-to-severe cases and are associated with cumulative toxicities such as bone marrow suppression and organ injury, underscoring an urgent need for precision-based interventions. This review synthesizes recent advances in molecular targeted therapy for IBD, clarifies mechanisms underlying key targets, and evaluates the efficacy and safety of emerging agents to inform clinical decision-making and future research. We performed a comprehensive literature search (2014-2025) in PubMed, Embase, and the Cochrane Library using keywords such as "inflammatory bowel disease," "molecular targeted therapy," "TNF inhibitors," "JAK inhibitors," and "biomarkers." This search identified over 500 clinical trials, meta-analyses, and mechanistic studies. The evidence highlights the transformative role of targeted agents in increasing remission rates while revealing variability in response across patient subgroups and uncertainties regarding long-term safety. Core issues include optimizing therapeutic sequencing to prevent primary non-response and secondary loss of response, validating and integrating biomarkers (e.g., miR-21) for stratified treatment, and balancing efficacy of multi-pathway modulators against risks such as opportunistic infections and cardiovascular events.
PMID:41350713 | DOI:10.1186/s12967-025-07385-3