2022 消化系聯合學術演講年會
專題討論（九） Impacts of the Tumor Microenvironment on GI-cancer Therapy IMPACTS OF THE PANCREATIC MICROENVIRONMENT ON ANTIPANCREATIC CANCER THERAPY 陳立宗 國家衛生研究院
Pancreatic cancer is a detrimental malignant disease. Aggressive tumor biology, relatively lack of specific symptoms/signs in early stage, the difficulty in detection by regular in-hand imaging facilities, such as abdominal ultrasonography, and the lack of awareness of the disease are all potential causes for the delay diagnosis of this highly malignant tumor. At time of diagnosis 80-85% of patients presented with unresectable locally advanced or metastatic diseases, while majority of the rest 15-20% of patients who underwent curative surgical resection would suffer from systemic and/or local relapse. However, in the era of precision medicine, only a small proportion of pancreatic cancer patients could benefit modern targeted and/or immunotherapy, such as those with tumor harboring germ-line BRCA1/2 mutation (maintenance PARP-1 inhibitor), and MSI-H or TMB-H(second-line anti-PD-1 inhibitor) Systemic chemotherapy, front-line FOLFIRINOX, nalpaclitaxel plus gemcitabine and S-1-based regimens, and second-line liposomal irinotecan plus infusion 5-FU/LV, remain the main treatment strategies for
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advanced pancreatic cancer in clinical practice setting. Without breakthrough improvement in the screening, diagnosis and management strategies, the progress in managing pancreatic cancer was slow with an overall 5-year survival rate of 8% globally. One of the unique pathological features of pancreatic cancer is the presence of a highly fibrotic tissue surrounding cancer cells, the desmoplastic stroma, which is conceived to attribute significantly to the aggressive biological behavior and chemo-/ radiotherapy resistance of the tumor. Unfortunately, several stromal targeting therapies, such as matrix metalloproteinases, hedgehog inhibitor, hyaluronidase, hypoxia-activating chemotherapy, and a bunch of immunotherapy have failed to demonstrate survival benefit for advanced pancreatic cancer in phase 3 trials. With the advance of modern biomedical technologies, the interactions among various stromal cells, immune cells and cancer cells are dissected more dedicatedly, which may provide the second chance for developing stromal-targeting therapy in pancreatic cancer.
