Checkpoints

Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects. Zachos, G. et al. EMBO J. 22, 713–723 (2003)

Chk1 is thought to initiate a checkpoint response to aberrant DNA structures, but its further study in multicellular organisms has been inhibited by the embryonic lethality of Chk1-deficient cells. Gene targeting has facilitated its deletion in the avian B-lymphoma DT-40 cell line; cells remain viable but have a defective checkpoint response and are sensitive to ionizing radiation. Chk1 seems to promote the survival of tumour cells by inhibiting mitosis, and its inhibition could therefore be a therapeutic target.

Gene profiling

Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling. Küppers, R. et al. J. Clin. Invest. 111, 529–537 (2003)

The tumorigenic cells of Hodgkin lymphoma are the Hodgkin and Reed–Sternberg cells, but they have been difficult to characterize. They originate from germinal-centre B cells and gene profiling has been performed to compare their gene expression with that of other normal and malignant B-cell types. They were found to be different to the other B cells and most like EBV-transformed B cells. Expression of several genes was specifically aberrant and these might represent targets for diagnostics and therapeutics.

Tumour progression

IL-1 is required for tumor invasiveness and angiogenesis. Voronov, E. et al. Proc. Natl Acad. Sci. USA (doi:10.1073/pnas.0437939100)

The role of IL-1 in tumorigenesis was assessed by transplanting different tumour types into Il-1α- and Il-1β-knockout mice. They found that melanoma, mammary adenocarcinoma and prostate tumours grew more slowly and were less likely to metastasize in the knockout mice than in controls. Il-1α and Il-1β were shown to contribute to tumour angiogenesis, but the role of Il-1β was more evident in these processes. The authors suggest that IL-1 antagonists might be effective anticancer therapeutics.

Drug targeting

Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels. Hallahan, D. et al. Cancer Cell 3, 63–74 (2003)

Treatment of cancers with ionizing radiation induces expression of neoantigens, and these proteins present a tumour-associated target for therapy. Post-translational modification of integrins, including the fibrinogen receptor α2bβ3 integrin, was induced by radiation and led to accumulation of these proteins within the tumour vasculature. Targeting irradiated tumours with fibrinogen-conjugated nanoparticles led to destruction of the vasculature and consequent tumour regression.