Cancer patients and their friends and families know that cancer chemotherapy is notoriously difficult and toxic to patients for a wide variety of reasons, and the big problem is to kill cancer cells while leaving the rest of the normal cells in the body alone. There are a few strategies to go around this problem. One popular strategy tries to create drugs that target something unique in cancer cells, and so affect tumor cells more than normal cells. Another strategy uses a “zoning agent”, like an antibody that binds to something specific on a cancer cell, to which the drug itself is attached, so that the drug reaches the cancer cell alone. A third strategy often uses agents such as liposomes (which are sacs made of fatty substances), which can penetrate the pores present in tumors (but also a few other organs). The drug is delivered within the liposome sac. Once they get in, they stick around, and the drug within is released, so can act on the tumor alone. However, all of these methods have some limitations.
But can biology provide tools and answers that will allow the combination of two or more of these different systems, to make the cancer drug even more specific and effective? There are numerous different efforts going on across various research groups, but this rather nifty way to answer this question, where some researchers have found their solution in a bacteria really caught my attention.
There is a large genus of bacteria called Clostridium, which includes some toxic ones that cause botulism (common in food poisoning) or tetanus or colitis (from diarrhea to death), while other species of this genus are harmless and non-toxic. Now, these bacteria are anaerobic, living in low oxygen areas. Most cancerous tumors have a “hypoxic” core (where oxygen levels are very low, due to excessive growth of cells, and a cutting off of blood supply). So, strains of clostridium would selectively infect this cancerous area. A strain of clostridium called C. novyi-NT (NT is non-toxic) also has a second property, in that it secretes something that disrupts lipid bilayers (which constitute the liposome). The researchers figured that this second property could also be used to improve drug release from liposomes.
So, combining this strategy, they infected mice with tumors with this bacteria, C. novyi-NT, AND liposomes containing an anti-cancer drug. If they injected the bacteria alone, or the liposome with drug alone, they only found limited therapeutic effects. But when they injected the bacteria as well as the liposome+drug, they saw dramatic therapeutic effects. All the infected mice showed reductions in tumor size, and 65% of them showed prolonged survival. Basically, C. novyi-NT dramatically improved the anti-tumor activity of the drug in cancerous mice. The bacterial treatment appeared to improve the distribution of the drug in cancerous tissues six fold, compared to just the liposome with the drug, while showing almost no effect on normal tissue.
The results are pretty striking, and actually do suggest the possibility of using such strategies (with this bacteria) in delivering anti-cancer drugs. The researchers also went one step further. They identified and characterized the specific protein in the bacteria that cause the liposomes to break. This actually provides even more strategies, where infection with the bacteria itself may not be required (you could for example attach this protein to a tumor targeting drug, and improve that drug’s efficacy).
A wonderful bit of research. You can read all about it in Science, 24 Nov 2006: Vol. 314. no. 5803, pp. 1308 – 1311