Targeted Therapy: Gene therapies
Cancer results from either the over expression of the oncogenes or the tumor suppressor genes becoming ineffective. The tumor suppressor genes which keeps a check on the development of cancer can be either defective or missing which results in the development of cancer. Gene therapy can be used either to block the oncogenes or replace the missing or the defective tumor suppressor genes. Gene therapy can also be used to make the conventional chemotherapy and the radiotherapy more effective against the cancer cells. It can also be used to protect the normal cells so that the conventional therapies can be used at a higher dose to destroy the cancer cells. Gene therapies are divided in to three groups.
- Replacing defective or missing tumor suppressor gene
- Blocking oncogenes
- Modification of the genetic information
Replacing defective or missing tumor suppressor gene
The tumor suppressor genes control cell replication. When this gene is missing or defective, the cells multiply indefinitely, causing cancer. The therapy involving replacement of tumor suppressor genes is still in the experimental stage and involves injecting the genes directly in to the cancer tissue. So far, results have not been uniform in tests.
Oncogenes are genes associated with cancer development. When mutated or over-expressed they can result in a malignancy. Agents used to fight this development include:
Antisense oligonucleotides – They are smaller synthetic pieces of DNA and RNA. They attach to complementary sites especially the messenger RNA in the tumor genes and prevent their expression. This controls the development and growth of tumors. But these agents are not very effective as they concentrate poorly in the cancer tissue.
Ribozymes – These are enzymes which are involved in cleaving the RNA and thus prevent the expression of genes. This is used mainly to cleave the RNA Bcr-Abl gene which is involved in chronic myelogenous leukemia. Again these agents have not proven effective as they concentrate poorly in the cancer tissue.
Modification of genetic information
Under this modality the genetic information of the cancer cells are modified to make them susceptible to conventional anti-cancer therapy and also to modify the genetic information of the normal cells so that they are protected against the effects of the conventional anti-cancer therapy.
This modality of treatment has three categories.
Immunomodulatory gene therapy – Tumor cells are retrieved, irradiated and transduced with cytokines like interleukin 2. When reintroducted, the tumor cells synthesize immunoregulatory cytokines, causing tumor rejection.
Suicide gene therapy – Specific viruses are used which infect only the cancer cells. This virus carries an enzyme with it. This enzyme converts the chemotherapeutic pro-drug in to active drug. So when then the conventional chemotherapy is given, it gets accumulated in the cancer cells where it gets activated and destroys the cancer cells.
Chemoprotection – Cells from the bone marrow are taken and transduced with genes to confer drug resistance and introduced back in to the patient. When conventional chemotherapy is administered, the patient's body better withstands the effects. Chemoprotection is still in the experimental stages.
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