Targeted therapy

Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas Li, D. et al. J. Clin. Invest. 117, 346–352 (2007)

Activating mutations of the epidermal growth factor receptor (EGFR) occur in many tumours, and some are resistant to current therapies. For example, the deletion of exons II–VII in the EGFRvIII mutant occurs in 5% of human lung squamous cell carcinomas. Kwok-Kin Wong and colleagues show, in a mouse model of lung cancer, that the monoclonal antibody 806, which recognizes a conformational epitope of EGFRvIII, induces the regression of tumours driven by EGFRvIII expression, indicating a promising therapeutic avenue for patients bearing this mutation.

Breast cancer

A common coding variant in CASP8 is associated with breast cancer risk Cox, A. et al. Nature Genet. 11 February 2007 (doi: 10.1038/ng1981)

The Breast Cancer Association Consortium analysed, in several large-scale case–control studies, nine single nucleotide polymorphisms associated with breast cancer. Although seven previously reported associations were not confirmed, two corresponded with reduced risk of cancer development. In particular, the caspase 8 (CASP8) D302H polymorphism, which results in an aspartic-acid-to-histidine substitution, protected against breast cancer in a dose-dependent manner. This work underlines the importance of large-scale studies to confirm and identify breast cancer susceptibility alleles.

Cancer stem cells

Identification of pancreatic cancer stem cells Li, C. et al. Cancer Res. 67, 1030–1037 (2007)

Diane Simeone and colleagues, using a xenograft model of human pancreatic adenocarcinomas, have identified a highly tumorigenic subpopulation of pancreatic cancer cells that show stem cell properties, such as the ability to self-renew and produce differentiated progeny. These pancreatic cancer cells — which express the cell-surface markers CD44, CD24 and the epithelial-specific antigen — generate tumours identical to those from which they originate with a much higher frequency than tumour cells that are negative for these markers. Characterizing this cell compartment could help to find more effective therapies for pancreatic cancer.

Leukaemia

Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia Fazi, F. et al. Blood 23 January 2007 (doi: 10.1182/blood-2006-09-045781)

Clara Nervi and colleagues identified a mechanism by which AML1 — the gene most commonly translocated in acute myeloid leukaemia (AML) — induces the differentiation block that is known to promote leukaemia development. The authors showed that AML1 recruits histone deacetylase, DNA methyltransferase and DNA-methyl-CpG binding activities to drive the epigenetic repression of retinoic acid receptor-β2 (RARβ2), a key mediator of the differentiation pathway induced by retinoic acid.