The role of RNA interference in targeting the cancer stem cell and clinical trials for cancer

Recently, compelling evidence has emerged in support of the cancer stem cell (CSC) theory for solid organ cancers. The CSC theory postulates that CSCs account for tumor initiation, tumor propagation, therapeutic resistance, and relapse following surgery or therapy. CSCs are able to do this through traits including (1) self-renewal, either through symmetric or asymmetric cell division via nonrandom chromosomal cosegregation; (2) the capacity for differentiation, which allows for the recapitulation of all cell types of the original tumor; and (3) tumor initiating capacity, which is the ability to propagate tumors when transplanted into a separate environment. The CSC theory provides better understanding of neoplastic formation and tumor propagation which may lead to novel exciting therapies for advanced cancer. Clear identification CSC-specific surface markers, genes (Nanog, Oct3/4, STAT3), and pathways such as TGF-β, hedgehog, and Wnt-β-catenin are crucial to the development of CSC-targeted treatments. RNAi provides a unique opportunity to silence cancer-causing stem cell genes at the pretranslation level, which is otherwise not possible with conventional therapies such as cytotoxic chemotherapy, small molecule inhibitors, or monoclonal antibodies. Owing to the explosion of knowledge generated by a growing understanding of the human genome and the development of high-throughput gene expression profiling of tissue stem cells, a plethora of genes that contribute to tumor initiation and the metastatic cascade are being discovered. RNAi therapy against multidrug resistance genes and CSC genes may provide exceptional benefit and herald a paradigm shift in the treatment of deadly diseases.