Introduction:


The ability of cancer cells to spread into other parts of the body is known as metastasis. This nature of cancer makes it difficult to treat and cure the condition in a patient. When the cancer is present in a particular site doctors can treat them or can be removed by doing some surgery. But once the cancer starts to spread throughout the body via biological fluids like blood or lymph, treatment becomes very difficult or impossible.

Some of the genetic alterations in the cell induce the primary tumor to spread into the body to produce secondary tumors. When these genetic alterations are stopped or reversed the process of metastasis of the cancer can be stopped.

Genetics of Cancer Metastasis:

1. During metastasis many changes in the cytoskeletal structure of cell have been seen. These changes are induced as a result of mutations in the genes which code for Rho and GTPase genes. These genes play major role in the regulation of actin filament, this in turn alter's the cancer cell motility.

2. Genetic mutations are also associated with the human colon cancer, where a normal proto-oncogene mutates into an oncogene. Proto-oncogene which codes for Ras protein, which controls the cell cycle by controlling the signal transductions involved in the cell cycle. Mutataion in Ras gene induces the formation of tumors.

3. Gene responsible for the metastasis of breast cancer in women have been discovered by a collaborative study conducted by Princeton University and The Cancer Institute of New Jersey. Gene Metadherin on chromosome 8 was present and active in around 30 to 40 percent of patients with breast cancer. When this gene is active, it helps the tumor cells to bind to the blood vessels, which are present in the distant organs of the body. This active form of gene also makes these tumors resistant to chemotherapy.

4. The Virginia Commonwealth University Institute of Molecular Medicine and VCU Massey Cancer Center Scientists discovered the melanoma differentiation associated gene-9/syntenin (mda-9/syntenine) which interacts with the signalling molecule to induce melanoma cells metastasis.

The gene melanoma differentiation associated gene-9/syntenin (mda-9/syntenine) interacts with c-Src signalling molecule, which helps in tumor cell growth and metastasis. The mda-9/syntenine activates the c-Src gene expression; this inturn increases the formation of signalling complex such as FAK/c-Src. This signalling complex increases the cancer cell motility, hence the metastasis.

Applications of Discovery of genetics involved in cancer metastasis:

1. Discovery of genes involved in cancer metastasis will help in designing new therapeutic drugs, which will suppress the development and dissemination of the tumor. Thereby will prevent the metastasis of tumors and localized form of tumors are easy to treat and hence will increase the survival rate of the cancer patients.

2. Disrupting or inhibiting the interaction between the gene mda-9/syntenin and c-Src may be used to prevent the spreading of primary tumor throughout the body. Research is going on to find out the small molecules which can be used to disrupt this interaction, therefore will prevent the cancer metastasis in patients.

3. By designing the drugs that target the genes responsible for cell division, cell mobility can be used to prevent the metastasis of cancer. This will make easy to treat cancer metastasis.

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