However, invariably these forms of therapy have a negative effect on the body. Chemotherapy and would result in a healthy cells getting destroyed. Surgery is not of great curative significance in leukemias only helping to remove the enlarged spleen. Biological therapy is of limited use in leukemias helping the body’s resistance to overcome the cancer cells. One of the best treatments for leukemias has been bone marrow transplant and stem cell transplant, in which the diseased bone marrow is removed and replaced with a healthy histocompatible one.
However, only a few cases are able to obtain histocompatible bone marrows and in several cases, there is a serious shortage of histocompatible bone marrow (Campbell 2009). A new form of therapy known as targeted cell therapy aims at destroying those molecules that are involved in converting the normal cells of the body to cancerous cells. The safety and efficacy of this form of therapy is being studied currently. However, scientists are not a huge lookout for effective, cheaper and safer means of treating leukemias (NCI 2009).
Apoptosis is a process by which cell death is programmed by a series of biochemical events leading to various morphological changes including blebbing, cell membrane changes, cell shrinkage, fragmentation of the nucleus, chromatin condensation, fragmentation of the DNA in the chromosomes, etc. A number events present can bring about the programmed cell death (PCD). Usually the apoptosis cell death would occur when the cell lives beyond its normal lifespan. Apoptosis can also be induced by specific cell to cell interactions specially FAS and FAS ligand binding.
In several cancer therapies, death receptor signalling has been utilised to induce apoptosis in the target malignant cells and in this way help cure the cancer. Another is the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) interaction with the specific receptor present on the cell (Plager 2008). TRAIL is basically a protein that has 281 amino acids and is also known as ‘APO2L’. There are five receptors present on the cell that are associated with TRAIL including RAILR1 (DR4), TRAILR2 (DR5/ TRICK2 or KILLER), TRAILR3 (DcR1/ TRID or LIT), TRAILR4 (DcR2 or TRUNDD), and Opg (Osteoprotegerin).
Apoptosis can be induced by TRAIL 1 and TRAIL 2 bringing about death. DcR1, DcR2, Opg act as decoy receptors binding TRAIL but not bringing about apoptosis (SAB Biosciences 2009). DcR1 has a TRAIL binding region and anchors the receptor to its membrane. However, the intracellular component is missing in DcR1, which brings about the destruction. DcR2 will combine with TRAIL but the death domain is condensed, not helping in apoptosis but activating the nuclear factor kappaB. Opg is weaker than TRAIL and combines with OpgL.
It activates NF-kappaB ligand but also increases the bone density through osteoclastic activity. The decoy receptors are present in larger number in normal cells, whereas the TRAILR1 and TRAILR2 are present in transformed cells. A normal cell is likely to bind with death ligands and survive (SA Biosciences 2009). If the TRAIL death receptors present on the cell are targeted then the cell would be stimulated to undergo apoptosis. Both the death receptors and the decoy receptors are targeted and hence selective destruction can be brought about.
As TRAIL has a shorter half-life than monoclonal antibodies, they have to be given frequently in larger doses to curb the cancerous cells. A few cells have shown resistance to TRAIL (Medscape Today, 2007). A study by Seol et al has demonstrated that Adenovirus infected TRAIL cancerous cells helps to get over the resistance offered to soluble TRAIL by inducing a media-transferable bystander effect. This helped to improve the therapeutic value (Seol, 2003).