European Journal of Cancer: Highlights of Issue 37:15

Current perspective of the new ‘magic bullet’ STI 571

With advances in the understanding of molecular and biological pathways, new selective and targeted drugs are being designed and tested. One such agent is STI 571. This drug is a highly selective, synthetic inhibitor of the protein tyrosine kinase family, a group of enzymes involved in the regulation of cell proliferation, growth and function. In this issue, Verweij and colleagues discuss current studies of its use in Chronic Myeloid Leukaemia (CML), Acute Lymphoblastic Leukaemia (ALL) and Gastrointestinal Stromal Tumours (GIST) patients. These studies show the drug to have activity with generally limited side-effects, although as Verweij and colleagues point out data on long-term effects are lacking and thus cumulative toxicity can not be assessed. The Food and Drug Administration (FDA) approved on May 9th this year its use in patients with CML and the authors, although urging caution in its widespread use until further experience has been acquired, state that ‘in their opinion, STI 571 is one of the most important agents recently developed’.

Use of a mistletoe lectin as an immunoadjuvant in IL-2-based therapy

Interleukin-2 (IL-2) therapy has been shown to be effective in a range of animal and human cancer models. However, such therapy is associated with a life-threatening side-effect known as ‘capillary leak syndrome’. The syndrome is characterised by rapid fluid accumulation in the tissue spaces and severe hypotension and is thought to result from an overproduction of nitric oxide (NO), as it can be ameliorated by the use of NOS inhibitors. Plant lectins, derived from mistletoe, have recently been proposed to have antitumour activities despite, at present, no clear clinical validation of such claims. Indeed, data from animal models have provided evidence of both detrimental and beneficial effects of these compounds. In this issue, Timoshenko and colleagues have examined whether the addition of a galactoside-specific lectin from Viscum album L., VAA, at non-toxic and immunostimulatory concentrations, is able to increase the anti-tumour and anti-metastatic properties of IL-2, without any increase in adverse side-effects. Their results suggested that the addition of VAA to IL-2 to treat C3L5 mammary adenocarcinomas in C3H/HeJ mice did not further decrease tumour growth and the number of metastases compared with IL-2 treatment alone. Moreover, VAA treatment alone resulted in an increase in these parameters compared with controls confirming that the translation of these compounds to the clinic should be viewed with caution.

A structural homologue of mitoxantrone with cytotoxic activity in cisplatin-resistant ovarian and osteogenic sarcoma cell lines

Imidazoacridinone C1311, a structural homologue of mitoxantrone, has potent activity in animal models and murine and human experimental models for colorectal cancer in vitro and is shortly to enter testing in clinical trials. In this issue, Zaffaroni and colleagues study the activity of this compound in two ovarian cancer cell lines, A2780 and OAW42, and one osteogenic sarcoma cell, U2-OS. They looked at the growth of these cell lines and their experimentally induced cisplatin-resistant sublines following a 1h incubation with the drug. They showed the drug had cytotoxic activity against these cells and also induced the accumulation of cells in the G2/M phase. Apoptosis was also induced in a small percentage of the U2-OS cell lines. The authors state that ‘their findings should stimulate further studies into the preferential targets of C1311 in human tumours’.

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