Immunotherapy

Nonredundant roles of antibody, cytokines, and perforin in the eradication of established Her-2/neu carcinomas. Curcio, C. et al. J. Clin. Invest. 111, 1161–1170 (2003)

A DNA vaccine that encodes ERBB2 (also known as HER2/neu) has been shown to stimulate immune rejection of established breast tumours in mice. Curcio et al. analysed this mechanism and showed that successful immunotherapy requires the actions of CD4+ and CD8+ T cells, CD1d-restricted natural-killer T cells, neutrophils, macrophages, antibodies, Fc receptors, IFN-γ and perforin.

Carcinogenesis

Immune enhancement of skin carcinogenesis by CD4+ T cells. Daniel, D. et al. J. Exp. Med. 197, 1017–1028 (2003)

Daniel et al. investigated the immune response during epithelial carcinogenesis in K14-HPV16 mice. Although pro-inflammatory CD4+ T cells were found to infiltrate tumours, they targeted the bacterial infections associated with dysplastic skin, rather than the cancer cells. Surprisingly, the ensuing inflammatory response promoted epithelial carcinogensis. Mice that lacked CD4+ T cells were found to have delayed neoplastic progression and a lower incidence of tumours, indicating that the inflammatory response can, in some instances, enhance neoplastic progression.

Target discovery

Identification of Down's syndrome critical locus gene SIM2-s as a drug therapy target for solid tumours. DeYoung, M. P et al. Proc. Natl Acad. Sci. USA 100, 4760–4765 (2003)

By combining data-mining and antisense technologies, DeYoung et al. have shown that the short Single Minded 2 (SIM2-s) gene — found in the Down's syndrome critical region of chromosome 21 — is expressed in certain solid tumours. Antisense SIM2-s caused growth inhibition and apoptosis in vitro, and inhibition of tumour growth in vivo. These findings have important implications for diagnosis and treatment of solid tumours, and could aid understanding of the cancer risk in Down's syndrome patients.

Prostate cancer

Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumours. Malins, D. C. et al. Proc. Natl Acad. Sci. USA 15 Apr 2003 (epub ahead of print)

Malins et al. have shown that the DNA of histologically normal prostate tissue changes with age. 42% of older men have structural changes that resemble those from primary prostate tumours; these are caused by age-related DNA damage. Importantly, this analysis could distinguish primary prostate tumours from which metastases had been identified, with a 90% sensitivity and specificity. This could help identify men at risk of developing prostate cancer, and the chances of metastasis of those who already have it.