Radiation and new molecular agents, part II: Targeting HDAC, HSP90, IGF-1R, PI3K, and Ras

Current research efforts in cancer therapeutics include the development of novel inhibitory agents that target molecular pathways involved in tumor growth and progression. Ultimately, many of these agents may prove most efficacious when combined with conventional cytotoxic therapies, including radiation therapy. Elucidation of the biologic pathways underlying radiation response has identified several targets involved in radiation resistance, providing rationale for combining these agents with radiation. Agents targeting single pathways, including EGFR, IGF-1R, PI3K, and Ras, have been studied alone and in combination with radiation. Although this strategy is increasingly supported by preclinical and clinical data, the single-target approach may be limited by such factors as tumor heterogeneity and genetic instability. Emerging approaches include multipathway-targeted therapy by either combining target-specific agents or using single agents that target multiple pathways, including HDAC and HSP90 inhibitors. These approaches reviewed herein hold promise for improved radiation therapy efficacy and, ultimately, improved patient outcome. © 2006 Elsevier Inc. All rights reserved.