Differentiation-inducing therapy for solid tumors

Treating malignant tumor through the induction of cell differentiation has been an attractive concept, but clinical development of differentiation-inducing agents to treat malignant tumor, especially for solid tumors has been limited to date. Nerve growth factor, all trans retinoic acid, dimethyl sulfoxide, active form vitamin D(3), peroxisome proliferator-activated receptorgamma, 12-0-tetradecanoylphorbol 13-acetate, hexamethylene-bis-acetamide, transforming growth factor-beta, butyric acid, cAMP, and vesnarinone are known to have a differentiation-inducing capability on solid tumors in vitro and/or in vivo. Moreover some of the differentiation-inducing agents have been used for treating patients with solid tumor, but the therapeutic effect of the differentiation-inducing agents on solid tumor is not strong when compared with that of conventional chemotherapeutic agents. However, because most of the differentiation-inducing agents can potentiate the effect of conventional chemotherapy or radiation therapy, combination of differentiation-inducing therapy with conventional chemotherapy or radiation therapy might be used as a second- or third-line therapy in patients with advanced cancer. Furthermore, analysis of the molecular mechanisms of the tumor differentiation therapy might provide selective and targeted molecules for novel cancer therapy.