Therapeutics

Synthetic small inhibiting RNAs: efficient tools to inactivate oncogenic mutations and restore p53 pathways. Martinez, L. A. et al. Proc. Natl Acad. Sci. USA 99, 14849?14854 (2002)

RNA interference is increasingly used to aid research by allowing the generation of functional knockouts. But can this technique be translated into the clinic to treat patients with cancer? Martinez et al. have constructed short interfering RNAs that can differentiate between wild-type and point-mutated p53. So, the mutant p53 ? in tumours that express wild-type and mutant protein ? could be selectively deleted, forming the basis of tailored therapy.

Diagnostics

Serum proteomic patterns for detection of prostate cancer. Petricoin, E. F. et al. J. Natl Cancer Inst. 94, 1576?1578 (2002)

At present, to confirm whether men with increased levels of prostate-specific antigen have prostate cancer or not, a biopsy sample must be taken. Petricoin et al. developed a bioinformatics algorithm that allowed discrimination between patients with prostate cancer and those with benign or no disease. The serum proteomic pattern correctly predicted 95% of patients known to have prostate cancer and 78% of patients with benign conditions.

Immunotherapy

Dual-specific T cells combine proliferation and anti-tumor activity. Kershaw, M. H., Westwood, J. A., & Hwu, P Nature Biotech. 20, 1221?1227 (2002).

Antitumour immunity requires T-cell activation, but tumour antigens are generally poor immunogens. To expand tumour-reactive T cells in vivo, Kershaw et al. generated dual-specific T cells that could respond not only to an immunogen, but could also recognize folate-binding protein (FBP) ? an antigen associated with ovarian cancer. Mouse dual-specific T cells responded to both allogeneic antigen and FBP-expressing tumour cells in vitro, and expanded in response to immunization with allogeneic cells in vivo. Human dual-specific T cells were also generated.

Therapeutics

Inhibitors of Ras/Raf-1 interaction identified by two-hybrid screening revert Ras-dependent transformation phenotypes in human cancer cells. Kato-Stankiewicz, J. et al. Proc. Natl Acad. Sci. USA 99, 14398?14403 (2002)

The signalling cascade that acts through RAS and RAF is activated in a significant number of tumours, so inhibiting their association is a viable therapeutic strategy. Small-molecule compounds that inhibit this interaction were identified using a two-hybrid approach. These prevented activation of the mitogen-activated protein kinase pathway and caused reversion of several RAS-transformed phenotypes, such as influencing morphology, invasiveness and anchorage-independent growth in a number of cell types.