Cure Cancer with TRAIL

Cancerous Cell
Cancer cells are notorious for their ability to detach themselves from tumours, flow through the blood stream and find themselves new sites in the body to adhere to and grow in size and number. Called metastasis, this process allows cancerous cells to not only survive in the body but also regroup at some other site, where you are least suspecting them to be and show up their ugly side as tumours. Site specific radiation therapy or even chemotherapy, for that matter, lacks the specificity to attack cancerous tumour alone, let alone freely floating cells and therefore, in spite of all advances in medicine and all the treatments that are offered to patients, there has never been a 'cure' for cancer. This, however, might soon change. 
In the mid 1990s, researchers Steven Wiley and his team at the Immunex Research and Development Corporation, Washington identified a new protein called TRAIL ( TNF-related apoptosis-inducing Ligand). The TNF family of proteins has been long associated with apoptosis or programmed cell death. Apoptosis is the mechanism by which an organism gets rid of problematic/unnecessary cells (self or foreign) in the body. (Every day, about 50 billion cells undergo apoptosis in an adult body). The TNF family of proteins perform a special function in our body by initiating the same process of apoptosis against tumorous cells, hence the name, Tumour Necrosis Factor. Naturally, TNF superfamily is one of the main ally of researchers world wide, looking into development of anti-cancer treatments. Further research on the TRAIL showed that the protein, secreted by normal cells, is capable specifically binding to cancerous cells on specific sites called the 'death receptors'. Once the TRAIL binds to a cell, it begins a chain reaction that finally results into the death of the cell. 

Many drug companies latched onto TRAIL as the ultimate cure for cancer and initiated studies to test the efficacy of the protein. TRAIL was used in combination with chemotherapy and yet clinical trials conducted gave mixed responses. What was worse was that repeated administration and exposure of TRAIL to tomourous cells, also seemed to confer some resistance to these cells, thereby reducing the efficacy of the drug. Although, there are many mechanisms proposed to explain TRAIL resistance, the fact remains that TRAIL is one of our best chances to check cancerous growth and needs to be administered with much more caution to patients and not be used in excess like antibiotics have been used in recent past.

The team of biomedical scientists in Michael King's lab in the Department of Biomedical Engineering at Cornell University decided to do exactly the same. Rather than bombarding tumours will large amounts of TRAIL, they decided instead to use it to attack the cause of cancer recurrence viz., tumorous cells that float freely in the bloodstream. Called Circulating Tumour Cells or CTCs, these cells use another protein called E-selectin to facilitate their adhesion to endothelial cells in the body and thereby forming new tumours. Luckily, E-selectin is also responsible for attracting leukocytes (white blood cells), our body's defending cells, to sites of injury or inflammation. What the researchers at Cornell managed to achieve was introduce nano particles into the blood stream with TRAIL on them. These nanoparticles were designed in such a way that they would bind to leukocytes after entering the blood stream.

Whenever CTCs attempt to adhere to cells, they need the assistance of E-selectin to complete the process, which will also bring leukocytes into the picture. With TRAIL by their side, these leukocytes can now easily recognize CTCs and flag them for destruction via apoptosis, thereby preventing them from adhering to endothelial cells. Eventually, all CTCs can be identified and destroyed the same way and the individual may indeed become free of cancerous cells. While preliminary studies in mice have shown this method to be extremely effective, there is still a lot more work to be done before this becomes a method to be used routinely. Nevertheless, the cure for cancer may be not that far away.

Sources: 

Mitchell MJ, Wayne E, Rana K, Schaffer CB, & King MR (2014). TRAIL-coated leukocytes that kill cancer cells in the circulation. Proceedings of the National Academy of Sciences of the United States of America PMID: 24395803

Steven R. Wiley, Ken Schooley, Pamela J. Smolak, Wenie S. Din, Chang-Pin Huang, Jillian K. Nicholl, Grant R. Sutherland, Terri Davis Smith, Charles Rauch, Craig A. Smith and Raymond G. Goodwin (1995). Identification and characterization of a new member of the TNF family that induces apoptosis Immunity DOI: 10.1016/1074-7613(95)90057-8

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