The Molecular Mechanism for Differentiation Therapy of Malignant Glioma

Gliomas are the most common malignant cancer affecting the CNS, accounting for 60% of primary brain tumors (DeAngelis, 2001; YiuH Bao et al., 2006). Additional considerations focus on developing novel modalities to increase anti-glioma effects and decrease side-effects. Differentiation therapy, using agents that modify cancer cell differentiation, has shown promise in the spectrum of agents used against tumors (Leszczyniecka et al., 2001). Wang and Chen demonstrated the clinical application for differentiation therapy by introducing all-trans-retinoic acid to clinical use for the treatment of acute promyelocytic leukemia (APL) (Huang et al., 1988; WangC Kinjo et al., 2000). Such excellent effects, however, were not reproduced in other hematological and, particularly, solid tumors. Differentiation agents for malignant gliomas remain a real challenge. In this chapter, we base on our research and mainly discuss proteins or molecules capable of inducing differentiation via targeting cAMP/cAMP-dependent protein kinase A (PKA) signal pathway and crucial factors such as glycogen synthase kinase-3┚ (GSK-3┚) and hypoxia-inducible factor-1┙ (HIF-1┙) determining the efficiency of these drugs. Although agents for differentiation therapy have wide application prospect, their real therapeutic potentiality remains to be further realized.