Therapeutics

Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc1+/−p53−/− mice. Romer, J. T. et al. Cancer Cell 6, 229–240 (2004)

Using a mouse model of medulloblastoma, Romer et al. showed that a small-molecule inhibitor of the sonic hedgehog (SHH) signalling pathway suppressed several genes that are highly expressed in medulloblastoma. This resulted in decreased tumour-cell proliferation, an increase in cell death and complete eradication of tumours. These findings support the development of SHH antagonists for the treatment of medulloblastoma.

Melanoma

Dead cells in melanoma tumors provide abundant antigen for targeted delivery of ionizing radiation by a mAb to melanin. Dadachova, E. et al. Proc. Natl Acad. Sci. 101, 14865–14870 (2004)

The pigment melanin is normally found in melanosomes, but Dadachova et al. hypothesized that in rapidly growing melanomas, melanin would be released from cells and could be targeted for delivery of cytotoxic radiation by antibodies against melanin. Treating mice bearing melanoma xenografts with such a therapy inhibited tumour growth and prolonged survival. The authors suggest that the radiation is delivered to adjacent viable tumour cells by bystander effects.

Mouse model

Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model. Uhrbom, L., Nerio, E. & Holland, E. C. Nature Med. 24 Oct 2004 (doi:10.1038/nm1120)

Eric Holland and colleagues have produced a novel transgenic mouse for imaging the loss of the retinoblastoma pathway and proliferative activity of glioma cells over time using a luciferase gene controlled by the E2F1 promoter. They show that platelet-derived growth factor (PDGF)-induced gliomas are dependent on both activation of the PDGF receptor and TOR signalling.