Next-Generation models of Gallbladder Carcinoma: Linking biological insights to precision medicine

Gallbladder carcinoma (GBC) is among the most aggressive and deadly malignancies of the biliary tract, with limited early diagnosis and treatment options largely due to a poor understanding of its complex tumor biology. Effective preclinical in vitro models are essential for advancing the understanding of its complex pathobiology and improving therapeutic strategies. Recent research has expanded experimental platforms for studying GBC biology beyond conventional two-dimensional (2D) cultures to include advanced three-dimensional (3D) systems, xenograft models, and emerging technologies such as organoids, microfluidic devices, and air-liquid interface platforms. These models enable detailed investigation of tumor growth, stromal interactions, angiogenesis, invasion, and cellular motility. However, while traditional platforms have provided foundational insights into GBC biology, next-generation models incorporating immune components and patient-derived tissues offer enhanced recapitulation of tumor complexity and predictive power for therapeutic screening. This review critically examines the evolution of GBC modeling strategies, compares their strengths and limitations, and highlights the translational potential of cutting-edge approaches. Particular emphasis is placed on innovations that integrate immune components into patient-derived organoid systems, highlighting how cutting-edge technologies are driving the transition toward precision oncology for GBC. This detailed analysis seeks to guide future research efforts and encourage the creation of more efficient, individualized treatment approaches for this complex disease.