Osteosarcoma (OS) is the most common form of primary bone cancer. Although its incidence is rare, this cancer, along with other primary bone cancers, can be particularly distressing because they more often than not affect children and adolescents. OS tends to have a poor prognosis and often does not respond well to current treatment options. In fact, the probability of therapeutic improvement in a patient has remained unchanged for decades, therefore there is great potential for development of novel therapies.

Although there are now many new potential therapies in development or in clinical trials for OS and other bone cancers, one important limitation has been the problem of inadequate delivery of the therapeutic drug into the tumour itself. Many drugs are administered by intra-venous injection and so rely on the blood supply to get to their target, however tumours have a poor blood supply. This means that tumours are poorly penetrated by drugs, and thus their efficacy can remain unsatisfactory.

We would like to produce a therapy for OS that is better targeted to tumours, and moreover, specifically directs its effects to tumour cells without affecting normal tissues.

We have developed an attenuated form of the bacteria Salmonella typhimurium that prefers to live in tumours rather than normal tissue (1), and these bacteria can be modified to produce therapeutic molecules that kill or alter tumour cells. Similar bacteria are considered safe, having already been used in patient clinical trials.

We propose to improve the anti-tumour effects of our bacteria by modifying them so that they produce ‘RNA interference’ (RNAi) molecules. These molecules prevent the production of a target protein in a highly specific manner, and bacteria producing them will reduce the level of this target when they invade cells. We will generate bacteria producing RNAi and use them to invade OS tumour cells, and reduce the levels of a chosen target molecule. This will be one that is well-known to be involved in the progression of bone cancers.

Current experimental therapies, including gene therapy, generally require intra-tumoral injection for effect. However, intra-tumoral injection for patients with OS would be a particularly unpleasant and invasive procedure, and even less desirable, considering that patients are mainly children. Our bacteria offer exciting potential as vectors that can efficiently deliver gene therapy to tumours by simple intra-venous injection.

We envisage that these bacteria will be invaluable in future cancer treatment, and our method should also be applicable in other bone as well as non-bone cancers.

Dr Teresa Coughlan, University of Nottingham