Blair Christopher A, Zi Xiaolin
Department of Urology, University of California, Irvine, Orange, CA 92868, USA.
Indian J Exp Biol. 2011 Nov;49(11):836-9.
Array of new targets for investigation as cancer therapeutics has great potential to grow as new splice-variants are identified and characterized in cancer cell-lines and tumor samples. Tumor-specific splice variants are being discovered at an increasing rate and their functions are also investigated in cancer progression. The tumor-specific splice variants whose expression patterns and activities are successfully characterized may become attractive targets for ablation or splicing modification. The extreme specificity of their expression suggests that a variant-specific treatment may allow for targeting of cancerous cells with minimal impact to healthy tissues. Clinical investigation of applying antisense oligonucleotides to down-regulate mRNAs that contribute to cancer cell survival and to modify splicing patterns in muscular dystrophy has shown promising results. These results show that antisense therapy may be applied effectively and safely in humans. As these treatment strategies continue to improve and novel tumor-specific splice-variants are identified, modification of splicing patterns will become an important field of investigation to develop more effective and safe cancer therapies.
随着在癌细胞系和肿瘤样本中发现并鉴定出新的剪接变体，作为癌症治疗手段的一系列新的研究靶点具有巨大的增长潜力。肿瘤特异性剪接变体的发现速度越来越快，其功能也在癌症进展过程中得到研究。那些表达模式和活性被成功表征的肿瘤特异性剪接变体可能成为消融或剪接修饰的有吸引力的靶点。它们表达的极端特异性表明，变体特异性治疗可能能够靶向癌细胞，同时对健康组织的影响最小。将反义寡核苷酸应用于下调有助于癌细胞存活的mRNA并改变肌肉萎缩症中的剪接模式的临床研究已显示出有希望的结果。这些结果表明，反义疗法可能在人体中有效且安全地应用。随着这些治疗策略不断改进以及新的肿瘤特异性剪接变体被鉴定出来，剪接模式的修饰将成为开发更有效和安全的癌症治疗方法的一个重要研究领域。
