Engineering New Cancer Treatments

Metastasis, the spread of cancer cells to new organs, generally signals a poor prognosis but detecting circulating tumour cells is both difficult and time consuming. US and Russian scientists have now described a way to magnetically capture circulating tumour cells in the bloodstream that has potential for the early diagnosis of cancer and the prevention of metastasis. Magnetic nanoparticles, which were functionalised to target a receptor commonly found on breast cancer cells, were shown to bind and capture circulating tumour cells in the bloodstream when injected into mice. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. The approach allows cancer cells from a large volume of blood to be concentrated in peripheral blood vessels by a magnet attached to the skin, potentially increasing specificity and sensitivity up to 1,000-fold compared to existing technology. The cells can then be removed by microsurgery for genetic analysis, or can be noninvasively eradicated directly in blood vessels by laser irradiation through the skin, which is safe for normal blood cells.

The study is published in Nature Nanotechnology.

In a separate study, published in the British Journal of Cancer, a non-pathogenic strain of Salmonella typhimurium has been used to deliver the cytotoxic protein, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) directly to solid tumours. S. typhimurium were engineered to secrete murine TRAIL under control of the radiation-inducible RecA promoter which activates when cells experience DNA damage. Common bacteria such as Salmonella and Escherichia favour the microenvironment of solid tumours over normal tissue and when the modified S. typhimurium were injected into mice with mammary tumours they localized to the tumour. After 48 hours, the bacteria had multiplied to about 10 million per tumour and the mice were exposed to a very low dose of γ-radiation. The resulting mild DNA damage (single-stranded breaks) activated RecA and initiated synthesis of TRAIL which is highly toxic to cancer cells. Mice that received two low dose radiation treatments had the best result since TRAIL clears quickly and its release must be regularly re-stimulated for best effect; repeated dosing with modified S. typhimurium in conjunction with low dose radiation improved the 30-day survival from 0 to 100%.

The researchers hope that, once the technique is fully developed, spatial and temporal control of the release of cytotoxic agents will provide enhanced efficacy while limiting toxicity.