European Journal of Cancer: Highlights of Issue 38:14

New directions in gene therapy

It has been proposed that the therapeutic efficacy of adenoviral vectors is limited by the inability to infect target tumour cells that express low levels of the coxsackievirus and adenovirus receptor (CAR). To explore this theory, Kim and colleagues have used two ovarian cell lines that differ only in their expression of an adenoviral receptor, thereby removing any confounding influence from the cellular background. They showed, in both in vitro and in vivo studies, that a deficiency in this receptor limited the efficiency of viral transfer. The authors conclude that their results suggest “that strategies to redirect adenoviruses to achieve CAR-independent infection will be necessary to realise the full potential of adenoviral vectors in the clinical setting”.

Metallothionein expression differs in the polypoid and depressed types of early stage colorectal carcinomas

The role of metallothionein (MT) is not fully understood in carcinomas. In this issue Kuroda and colleagues have examined by immunohistochemistry the expression of MT in 87 colorectal adenomas and 128 early stage (T1 and T2) carcinomas. MT expression decreased significantly with tumour development suggesting that MT expression may be an early event in colorectal carcinogenesis and positivity was significantly associated with the depth of invasion (T1 60% vs. T2 33%), vascular involvement (positive 35% vs. negative 61%) and morphology (polypoid 62% vs. depressed 26%). Different patterns of MT expression were observed in the polypoid versus the depressed types and the authors speculate that this may be due to genetic differences between these two types.

Clinical response-its value and interpretation?

Clinical response is evaluated by pre-defined criteria (WHO/RECIST). In this issue, Dr. Therasse discusses (in a position paper based on his presentation at ECCO 11) how this parameter is presently used to help in the decision-making process with regard to continuing or stopping treatment. He examines the large variations seen in the response rates and discusses likely causes such as selection, random variations, precision in measurements. The use of different versions of the WHO criteria has also complicated comparisons between studies and prompted the development of the RECIST criteria published in 2000. Dr. Therasse points out that the development of new agents that act by differing mechanisms to those seen with the previous cytotoxics will require changes in how we evaluate response, with stabilisation and/or time to progression perhaps becoming more important. Examples include the tyrosine kinase inhibitor, STI-571, currently being used in the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GISTs) (see EJC news 2002 38:11). However, as an indicator of survival, the value of a clinical response is as yet unclear. Dr. Therasse also believes that functional imaging studies will be important in the future to provide an early indication of the anti-tumour activity and that most of the techniques developed will still require validation with regard to interpretation of the “response to treatment”.

Back . . .