Chinnaiyan Prakash, Allen Gregory W, Harari Paul M
Department of Human Oncology, University of Wisconsin Medical School, Madison, 53792-0600, USA.
Semin Radiat Oncol. 2006 Jan;16(1):59-64. doi: 10.1016/j.semradonc.2005.08.008.
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.
目前癌症治疗领域的研究工作包括开发新型抑制剂，这些抑制剂靶向参与肿瘤生长和进展的分子途径。最终，许多这类药物与包括放射治疗在内的传统细胞毒性疗法联合使用时，可能会被证明是最有效的。对辐射反应潜在生物学途径的阐明已经确定了几个与辐射抗性有关的靶点，这为将这些药物与辐射联合使用提供了理论依据。针对单一途径的药物，包括表皮生长因子受体（EGFR）、胰岛素样生长因子-1受体（IGF-1R）、磷脂酰肌醇-3激酶（PI3K）和Ras，已经单独进行了研究，并与辐射联合使用。尽管这一策略越来越多地得到临床前和临床数据的支持，但单一靶点方法可能会受到肿瘤异质性和基因不稳定性等因素的限制。新兴的方法包括通过联合靶向特定靶点的药物或使用靶向多种途径的单一药物进行多途径靶向治疗，包括组蛋白去乙酰化酶（HDAC）和热休克蛋白90（HSP90）抑制剂。本文所综述的这些方法有望提高放射治疗的疗效，并最终改善患者的治疗结果。
