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. We are investigating the molecular mechanisms for telomere maintenance, cell immortality, and cancer stemness. Based on these basic researches, we are also developing innovative druggable seeds. First, we are developing telomere-targeting drugs, such as G-quadruplex (G4) ligands, which stabilize G4s, unusual higher-order nucleic acid structures in the genome, and preferentially attack glioma stem cells and other intractable cancer. Second, we are developing chemical inhibitors for the poly (ADP-ribose) polymerase called tankyrase. This enzyme promotes telomere elongation by telomerase and Wnt/β-catenin signaling in cancer. Third, employing functional genomics and comprehensive gene expression and single-cell analyses, we are pursuing therapeutic molecular targets of cancer stem cells.