Year: 2026
Type: review
Abstract: Liver and lung metastases in pancreatic ductal adenocarcinoma (PDAC) differ in timing, molecular features, and clinical course. We propose that these differences emerge through five interacting processes: pre-existing predisposition, anatomical delivery, premetastatic conditioning, organ-specific selection, and adaptive colonization. This narrative review integrates clinical observations with genetically engineered mouse models (GEMMs), lineage tracing, and functional perturbation to explain liver-lung divergence. The framework organizes organ preference around the states available before dissemination, the cells delivered to each organ, and their subsequent survival and growth. It connects each process to an experimental readout, allowing recurrent-site associations and causal mechanisms to inform a common biological question. GEMM studies reveal early dissemination, heterogeneous metastatic competence, polyclonal seeding, and changes in tumor-cell and stromal organization across metastatic lesion sizes. Genetic manipulation of epithelial adhesion and tissue-specific signaling further identifies distinct requirements for hepatic and pulmonary colonization. Complementary transplantation experiments demonstrate organ-dependent responses to SMAD4 restoration and PCSK9 perturbation. Together, these findings support a probabilistic interpretation in which the same tumor-cell program can confer different advantages according to the target organ and stage of progression. Clinical recurrence patterns provide a complementary view of this biology, with isolated pulmonary disease often associated with a more indolent course. By linking evidence to the process it measures, the framework identifies opportunities to reduce dissemination, disrupt organ conditioning, or inhibit established metastatic growth and guides the design of prospective studies of organ-specific risk and treatment response.
Source: Cancer Management and Research
DOI: 10.2147/cmar.s644548
Authors: Baodan Cong, Kunfei Deng, Yu Du, Kaidi Sun
Institution: First Hospital of China Medical University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,836
OpenAlex ID: W7224299083