Therapeutics

A combinatorial approach for selectively inducing programmed cell death in human pancreatic cancer cells. Su, Z. et al. Proc. Natl Acad. Sci. USA 98, 10332–10337 (2001) [PubMed]

Pancreatic cancer is one of the leading causes of cancer death, and one of the most difficult to treat, but a new strategy that combines two independent treatments — expression of MDA7 and antisense antibodies that target the oncogene KRAS — is now showing promise. Pancreatic cells are resistant to MDA7 expression, which induces growth arrest and apoptosis in other tumour types. However, KRAS antisense treatment sensitizes cells to MDA7 expression, and apoptosis ensues through upregulation of BAX.

Diagnostics

Bioassay of prostate-specific antigen (PSA) using microcantilevers. Wu, G. et al. Nature Biotechnol. 19, 856–860 (2001) [PubMed]

A great challenge to diagnostics is high-throughput, quantitative protein detection. Wu and colleagues have used microcantilevers — tiny platforms that deform when proteins bind — to detect prostate-specific antigen (PSA), a marker for prostate cancer. Coating the microcantilever surface with antibodies to PSA allows wide ranges of unlabelled PSA to be detected in high concentrations of serum proteins. The technique could be applied to any protein, and lends itself to detecting many different proteins in parallel.

Gene therapy

A hepatocellular carcinoma-specific adenovirus variant, CV890, eliminates distant human liver tumours in combination with doxorubicin. Li, Y. et al. Cancer Res. 6, 6128–6136 (2001) [PubMed]

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death. α-Fetoprotein (AFP), a tumour marker used to diagnose this cancer, is expressed by HCCs but rarely by normal hepatocytes. Using the AFP transcriptional regulatory element to control expression of an oncolytic adenovirus, the authors created a vector — CV890 — to specifically target HCC cells. CV890 only replicated in and destroyed AFP-producing HCC cells, and reduced the growth of HCC in mice. Combination of CV890 with doxorubicin demonstrated synergistic antitumour efficacy. These findings support the development of this oncolytic vector for treating HCC.

Animal models

HVMNE, a novel lymphocryptovirus related to Epstein–Barr virus, induces lymphoma in New Zealand White rabbits. Ferrari, M. G. et al., Blood 98, (in the press)

Whereas DNA viruses such as Epstein–Barr virus (EBV) have long been associated with B-cell cancers, they have also been reported to cause T-cell malignancies. But their role in tumorigenesis remains controversial. HVMNE is a novel EBV-like virus isolated from macaques with a T-cell lymphoma. The authors show that this virus causes malignant T-cell lymphoma in New Zealand White rabbits. T cells from the animals were found to carry viral DNA, acquire interleukin-2 independence and constitutively activate the JAK/STAT pathway. This is a valuable new T-cell lymphoma animal model.