Genetics

CDX2 polymorphisms, RNA expression, and risk of colon cancer. Rozek, L. S. et al. Cancer Res. 65, 5488–5492 (2005)

The intestinal-epithelial-cell transcription factor CDX2 is often downregulated in colorectal cancer. But epidemiological and gene-expression data analysed in this study did not implicate common CDX2 variants in susceptibility to this disease. CDX2 expression levels did, however, correlate with microsatellite instability and tumour location, indicating a role for CDX2 in the specification of human gastrointestinal cell fate.

Cell cycle

CDK inhibitors uncouple cell cycle progression from mitochondrial apoptotic functions in DNA-damaged cancer cells. Le, H. V., Minn, A. J. & Massagué, J. J. Biol. Chem. 6 July 2005 (10/1047/jbc.M504689200)

The efficacy of DNA-damaging anticancer agents is severely reduced if cancer cells avoid apoptosis and, instead, enter cell-cycle arrest. The results presented here help clarify the relationship between cell-cycle-progression and apoptosis during therapeutic responses, and have important implications for the effective therapeutic combination of agents that affect the cell cycle with agents that cause DNA damage.

Stem cells

Identification of bronchioalveolar stem cells in normal lung and lung cancer. Kim, C. F. B. et al. Cell 121, 823–835 (2005)

A stem cell population that has been identified and isolated from the lung represents a possible target for the fight against some lung cancers. The research group, led by Tyler Jacks, called these cells bronchioalveolar stem cells (BASCs), after their location in the bronchioalveolar duct junction. Not only do BASCs have self-renewal and multipotent properties, they also proliferate in response to oncogenic K-RAS, both in vitro and in vivo. The authors conclude that the transformation of BASCs might give rise to adenocarcinomas.

Chemotherapy

The optimal biological dose of metronomic chemotherapy regimens is associated with maximum antiangiogenic activity. Shaked, Y. et al. Blood (10.1182/blood-2005-04-1422).

The remarkable efficacy of 'metronomic' chemotherapy — in which therapy is given regularly and frequentlyin low, non-toxic doses — is thought to be due to its anti-angiogenic effects. This has now been verified by Shaked et al., who have also identified a possible new assay for determining the 'optimal biological dose' (OBD) of metronomic chemotherapy. They found that the OBD in several preclinical tumour models correlated well with the number of circulating peripheral blood endothelial precursors that express vascular endothelial growth factor receptor 2.