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Manipulation of Anthrax to Deliver Cancer Drugs to Tumours

Cancer is acknowledged as one of the most dangerous biological diseases and there are many ongoing research studies to try and find suitable drugs to cure the uncontrollable cell replication. Cancer is caused when cells replicate unusually and rapidly to form tumours, this is because the cell does not undergo apoptosis (the normal programmed cell death) and these tumours need to be treated so that the disease does not further spread to the rest of the body and so that the tumours do not cause pressure on other parts of the body.[1] In 2008 breast cancer was responsible for the death of about 153 women in every 100,000 women in the population [1] and about 76 cases of lung cancer per 100,000 men.[1] These statistics have led to an escalation in the development of new treatments in an attempt to impede the uncontrolled cell replication typical of cancer cells.



It’s getting increasingly difficult to transfer drugs to their target site (the tumour), alternatively anthrax bacteria is very good at reaching cells but it also exudes a toxic product into healthy cells and kills them, making it a potent bacteria. However scientists want to find a way to exploit anthrax’s ability to go to the correct cells and use it to transfer anti-cancer drugs to tumours and inside them, removing the toxic product from anthrax and using only the “outer shell” of the bacterium, minus the toxins.

Anthrax bacterium is made up of three main components: Protective Antigen protein, which binds to the receptors TEM8 and CMG2 that are located on most mammalian cell surfaces. Protective Antigen protein binds to receptors on the cell surface to form a docking site for two anthrax proteins called Lethal Factors (LF) and Edema Factor (EF). These proteins are then pumped into the cell through a narrow pore and disrupt the cell reactions and growth therefore resulting in cell death.

The team of scientists working on the anthrax study replaced LF and EF proteins, which are the cause of anthrax’s toxic properties, with safe antibody mimics which observe the same purpose and enter the cell through the Protective Antigen channel.

Antibody mimics are a great advance in cancer research because they help to aid the transport of cancer drugs to the target site. The antibody mimics copy the protein structure which can be designed to target different proteins inside a cell. This study managed to manipulate the proteins to destruct chronic myeloid leukaemia. The scientists also were successful in blocking hRaf-1, the overactive protein in many cancers.

This research opens a door to cancer research and is now being tested in mice to test the success of these findings in vivo; to also define a way to deliver specific drugs to specific types of cell.

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Reference:

[1] Cancer Research UK (26 March 2010) Incidence, survival and mortality, Available at:http://cancerhelp.cancerresearchuk.org/about-cancer/what-is-cancer/statistics/incidence-survival-and-mortality#mortality (accessed: 04th October 2012).
[2] Xiaoli Liao, Amy E. Rabideau, Bradley L. Pentelute. Delivery of Antibody Mimics into Mammalian Cells via Anthrax Toxin Protective Antigen. ChemBioChem, 2014; DOI: 10.1002/cbic.201402290



Comments

  1. The antibody mimics can copy the protein structure,which means that protein can be personalized to target different cancer cells and treat cancers. It may be just hypothesis now, it is believed that this will promote the development of cancer therapy in future.

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