The abnormal growth of cells leads to the formation of a tumor. Some of these primary tumors become invasive and spread to sites other than their origin - such a phenomenon is known as metastasis. For example, the spread of breast cancer cells to the lungs resulting in lung cancer. Metastasis ultimately forms secondary tumors, also known as malignant tumors. The invasiveness of cancerous cells is heightened if the target tissue produces growth factors and angiogenesis factors. To select and design a particular therapeutic drug to control the spread of metastatic cells requires insights into the alterations of the genetic control of cells. To understand the cause of metastasis, multi approach studies such as the use of animal models and cell cultures have been conducted.
Various changes in the cytoskeletal structure of cells (their internal framework) have been observed in metastasis. These modifications are the result of mutations in the Rho and GTPase encoding genes which produce proteins that play important roles in the regulation of actin filaments. It is these changes that are believed to alter a cell's motility.
Another example of a mutation associated with metastatic cancer has been reported in human colon cancer wherein a proto-oncogene from a normal cell transforms into an oncogene. A Ras protein product of a proto-oncogene controls the signal transduction pathways involved in the cell cycle. Ras protein is activated by growth hormone signals and exists in two states. One is "on" or active state bound with GTP and the other is "off" or inactive state.
An alteration in a Ras gene leads to the accumulation of active Ras protein in the cell by reducing the rate of GTP hydrolysis and thus promoting the indefinite growth of cells. Such mutations alter proto-oncogenes to become oncogenes and initiate tumor formation. Oncogenic protein product have shown to transform the normal cell cultures into tumors cells.
Another study collaboratively conducted by Princeton University and The Cancer Institute of New Jersey has discovered the gene responsible for the metastasis of breast cancer. Approximately 30 to 40 percent of patients suffering from breast cancer showed the presence of a gene Metadherin on chromosome 8. When it is switched on it helps tumor cells stick to blood vessels in distant organs. It also makes tumors more resistant to chemotherapy. Discovery of this gene will open the door to the design of new therapeutic drugs to suppress the development as well as the dissemination of the tumor. Thus prevention of the spread of the tumor and its localization may help the survival rate of patients.
The major difficulty in the treatment of metastasis is the invasive nature of the cancer. Thus, the principle target is to prevent the spread of the cancerous cells by breaking the cycle of division of these cells, and that could be achieved by designing drugs that affect the genes involved in the cell cycle.