Div of Experimental Chemotherapy, Cancer Chemotherapy Center, JFCRAbstract公益財団法人がん研究会がん化学療法センター基礎研究部― 190 ―Remarkable progress has been made in molecularly targeted drugs for lung cancer, but acquired resistance is still a major problem, and it is difficult to achieve complete cure of cancer with targeted therapy. To develop the resistant tumor, there must be a small number of residual tumor cells after the targeted therapy, even it is effective and induce marked tumor shrinkage. Therefore, it is necessary to understand the microenvironment of residual tumors, especially the tumor microenvironment including immune cells, which leads to the emergence of acquired resistance, and to discover new therapeutic strategies based on the molecular basis of this microenvironment. This study has aimed to understand in detail the cancer microenvironment including immune cells in the residual tumor of molecularly targeted drugs and to develop new treatment methods, focusing on lung cancer with driver oncogene-positive cancers. To enable the analysis of residual tumor after molecular targeted drug, we used the following tools to analyze; (1) patient-derived primary tumor cells without long-term culture, (2) patient-derived cancer cell xenograft model, (3) syngeneic mouse xenograft models. Using the above models, we performed the detailed analysis of the residual tumor cells, CRISPR/Cas9 screening to identify the genes related to the drug-tolerant persister cells, and microenvironment analysis of the residual tumor in the mouse xenograft.Specifically, we obtained fresh clinical samples from patients with EGFR mutation-positive lung cancer and patients with ALK and ROS1 fusion gene-positive lung cancer prior to or approximately 2 weeks after initiation of molecularly targeted drugs, mainly pleural effusions, to establish patient-derived cancer cell lines and also 宿主免疫細胞と間質細胞の役割と新規複合療法の探索Analysis of tumor immune microenvironmentがん分子標的療法残存腫瘍におけるin the drug tolerant tumor remainingafter molecular targeted drug treatment片山 量平Ryohei Katayama
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