**2. Cancer is a complex genetic disease**

It has long been suggested that the cancer has evolved from a single cell transformed by the influence of the environmental factors such as physical, chemical factors, and viruses. Changes in hundreds of genes, so-called mutations, are required to transform a normal cell into a cancer cell. The major functional changes that transform a cell are mainly the activation of oncogenes or inactivation of tumor suppressor genes.

The overexpression of oncogenes and loss of function of tumor suppressor genes usually induce malignant transformation. Those changes are also required for further growth of tumor cells.

A transformed cell usually gains some important biological properties to establish a malignant disease. Those properties, including uncontrolled proliferation, evasion of growth suppres‐ sors, inhibition of apoptosis, replicative immortality, angiogenesis, proliferative signals, invasion, and metastasis, are discussed in detail in a recent review of Hanahan and Weinberg [1]. Although the conventional chemotherapy has mainly focused on direct tumor cell killing, a vast majority of current targeted therapies have aimed to eliminate one or more of the abovementioned properties of cancer cells.

The targeting of angiogenesis, proliferation pathways, and immune system has yielded a number of drugs that are already in the market. Nodules of cancer cells cannot grow beyond 1–2 mm without expanding their blood supply to access every increasing need for oxygen and nutrients. In order to generate the additional blood supply, the tumor tissue stimulates the elaboration of its own vessel network, through a process called angiogenesis [2]. If one could cut the blood supply of the tumor, it cannot grow beyond 1–2 mm, which means that they cannot grow enough to be diagnosed by the current diagnostic technology and cannot cause a clinical disease. The tumor vascular targeting therapy or antiangiogenetic therapies like bevacizumab and aflibercept targeting ligands of angiogenesis or small tyrosine kinase inhibitors of angiogenesis pathway receptors or signaling molecules have already emerged as standard therapeutic drugs in various tumors [3].

The overexpression of oncogenes and the loss of function of tumor suppressor genes are usually involved in both malignant conversion of the cells and further growth of tumor cells. A new generation of small molecules targeting proliferation pathways, like gefitinib, erlotinib, and imatinib, has been developed to block the cancer-causing signals within cancer cells and become standard treatments in those patients with mutations of EGFR or c-KIT [4]. Antibody molecules, targeting the EGFR family of receptors like trastuzumab, cetuximab, and panitu‐ mumab also block the growth-promoting signals that push cancer cells into an unregulated pattern of growth [5]. In contrast to standard chemotherapy, which is quite damaging to the normal tissues of the body as well as the cancer tissue, the targeted drugs are quite specific for the cancer cells and therefore relatively free of side effects.

Although majority of the cancer patients has a fairly intact immune system, the cells of the immune system do not usually respond to tumor cells because the immune system cannot differentiate the normal and cancer cells and therefore cannot fight against them. Immuno‐ therapy or cancer vaccine therapy aims to activate immune system against tumors. Recently, ipilumumab/tremelimumab and pembrolizumab/nivolumumab targeting checkpoints of immune response such as CTLA-4 or PD1 have also been approved [6]. Likewise, a dendritic cell-based vaccine, sipuleucel T, for the treatment of metastatic prostate cancer has been approved 2 years ago [7].

Hundreds of genes have been involved in the action and regulation of those pathways. The generation of cancer through a series of changes in the normal cellular genes makes the disease a genetic disease at the cellular base. The involvement of genes in the development of the disease also makes the disease a good candidate for gene therapy. Therefore, gene therapy has emerged as the hope of curative treatment modality in cancer.
