Japanese Foundation for Cancer Research

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16Research ProjectsThe aim of this research division is to identify possible targets, to clarify their function, and ultimately to develop an effective molecular-targeted therapy for cancer. For this purpose, we are investigating the molecular mechanisms of acquired resistance and developing anti-metastatic drugs targeting our identied Aggrus/podoplanin protein. Our mission is to contribute to cancer chemotherapy by creating new molecular-targeted drugs. To this end, we established a panel of cancer cell lines (JFCR39) and an accompanying database, which helps us to identify anti-cancer compounds and their molecular targets. Actually, ZSTK474, a PI3K inhibitor, has been evaluated in clinical trials.Unusual maintenance of chromosome ends, telomeres, supports infinite cancer cell growth. This system will also support so-called cancer stem cells, which contribute to initiation, metastasis, and recurrence of the disease. This laboratory investigates the molecular mechanisms for telomere maintenance and cancer stemness, and develops druggable seeds for eradication of cancer.Our research interests are to identify new molecular targets for tumor-selective therapy and to identify biomarkers for predicting drug responsiveness in cancer patients. Using genome technologies, we promote two projects: 1) basic research for microenvironment-oriented, molecular-targeted therapy, and 2) translational research for diagnosis of drug responsiveness in molecular-targeted therapy.The molecular targeting drugs, imatinib (ABL-kinase inhibitor), rituximab (anti-CD20), improved prognosis in leukemia and lymphoma. We investigated resistance mechanism using clinical samples under IRB approval. We discovered CD20 mutation, and up-regulated gene in leukemia after exposure of imatinib, proteasome inhibitor resistant myeloma cell line under investigation using GFP-ADCC.●Division of Experimental ChemotherapyAnalysis of acquired drug resistance and tumor metastasis●Division of Molecular PharmacologyDiscovery and development of novel molecular-targeted anti-cancer drugs ●Division of Molecular BiotherapyTelomeres, cell immortality and cancer stemness as therapeutic targets●Division of Genome ResearchGenome science-driven research for targeted therapy●Division of Clinical ChemotherapyAnalysis of drug resistance and molecular target by imaging technologyIn addition to our solid basic research, the Cancer Chemotherapy Center focuses on “Translational Research (TR)�? and “reverse TR�? to apply research ndings to clinical practice and to obtain new knowledge from clinical cancer specimens by collaborating with physicians, pathologists, and basic researchers under IRB approval. To apply the findings for better future cancer therapy, we are developing anti-metastasis drugs (neutralizing antibody and low-molecular-weight compounds) targeting Aggrus protein discovered in basic research. We are also developing compounds called G-quadruplex ligands, which can target patient-derived glioma stem cells. 　Recently, various novel molecular targeting agents have been developed for cancer chemotherapy. However, resistance in treatment-naïve cancer or acquired resistance is a life-threatening problem for cancer patients. We thus examine the residual tumor specimen for understanding molecular mechanisms of resistance against molecular targeted therapy, and the characteristics of cancer stem-like cells (CSCs).

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