Radiation therapy has been a mainstay of cancer treatment for over a century, and in that time has saved the lives of countless patients, but at high doses can have serious side effects when it damages healthy tissue as well as killing cancer cells. A study published this week in the journal Science (1) describes a new drug that may help reduce these side effects, by activating a pathway that stops healthy cells exposed to radiation from initiating a process of programmed cell death.
A bacterial protein named flagellin can bind to and activate TLR5, a cell surface receptor that in turn activates a protein called NF-kappaB that is known to protect against radiation damage. The scientists lead by Dr Andrei Gudkov tested whether flagellin could protect mice against otherwise lethal doses of radiation. They observed that flagellin could protect the mice, but also that flagellin has undesirable side effects, so they next engineered a series of molecules based on flagellin and tested them for their ability to protect against radiation and whether they caused side effects. Tests in mice indicated that one of the molecules, named CBLB502, could protect against radiation as well as flagellin but without the side effects, and follow on studies also indicated that it was safe and effective in monkeys.
Of course if CBLB502 is to be useful in reducing radiation damage in cancer patients it is also vital that it doesn’t interfere with the ability of radiotherapy to kill cancer cells. The ability of radiation to shrink tumours in mice treated with CBLB502 was compared to that in untreated mice, and no difference was observed between the two groups, indicating that CBLB502 will not interfere with radiotherapy.
These results are very promising, and clinical trials in cancer patients are expected to begin soon. This drug may not only reduce the side effects of radiotherapy but also enable doctors to use higher radiation doses when treating patients than is currently possible. As discussed in news reports CBLB502 may also be useful when treating people exposed to radiation due to an accident or terrorist attack.
Animal tests indicate that it must be administered within an hour of exposure to be of benefit, which may limit its use in large incidents when many people are exposed, but it could be given to people at risk of radiation exposure or kept in readiness at workplaces where radioactive materials are present.
In other news the Wellcome Trust has published its annual report for 2007, available at http://www.wellcome.ac.uk/About-us/Publications/Annual-review/index.htm. Among many other topics it includes several examples of where animal research is advancing medical knowledge, for example in the development of a new class of antibiotics known as the lantibiotics. The report provides an excellent overview of the varied activities of the UK’s largest medical research charity and is well worth a read.
1. Burdelya L.G. et al. “An agonist of Toll-Like Receptor 5 has radioprotective activity in mouse and primate models” Science Vol. 320, no. 5873, pages 226-230, DOI: 10.1126/science.1154986