Abstract: In the past two decades, approximately 1000clinical cancer trials based on gene drugs have been reported on or were carried out. These trials used a variety of genes and vectors, and involved almost all kinds of tumor types. How-ever, the sustaining curative effects of gene medicine needed further study. One important reason for this phenomenon was the lack of systemic knowledge about cancer itself. Carcinogenesis is a result of a multi-gene, multi-factor and multiple step process. Recent results have shown that the genetic alterations of a large number of genes functioned through a rela-tively small number of pathways and processes. Both concurrent and mutually exclusive mutations were found in cancer. The concurrent mutations were easy to understand, while the exclusive mutations were supported by the evidence of EG-FR mutation and K-ras mutation. The mutant ratio of EGFR and K-ras was high in lung adenocarcinomas; however, few pa-tients exhibited both mutations simultaneously. The theory of “Oncogene addiction ”may provide a likely explanation for exclusive mutations. In its simplest form, oncogene addiction refers to the curious observation that a tumor cell, despite its plethora of genetic alterations, can seemingly exhibit dependence on a single oncogenic pathway or protein for its sus-tained proliferation and/or survival. Therefore, the best hope for therapeutic development may lie in the discovery of agents that target the physiologic effects of the altered pathways and processes rather than their individual gene components. So, targeting to the dysregulated genes with synergetic effects, such as microRNA or multi-gene therapy, may provide better success for cancer gene therapy.