Drugs that target malignant cells close to market

Iressa, an Astra Zeneca drug now in phase III trials

In the past, drug therapies have failed to capitalise on the inherent differences between malignant and non-malignant cells.  Hardly surprising, because so little was known about the way in which tumours behave at the cellular level.  This subject has been the focus of intense research over the past decade or so.  It has led to the possibility of designing drugs which seek out cancer cells and ignore normal healthy cells in the body.

Drugs which interfere with this signal pathway are designed to stop the cells growing and proliferating.  They may also inhibit many of the other unpleasant features of malignant cells such as angiogenesis - encouraging blood vessels to grow and support the cancer, metastasis - cancerous cells moving to other locations in the body, apoptosis - cells not dying off as normal cells do and evolution to forms resistance to both radio and chemotherapy.  Because the drugs are specifically aimed at the cancerous cells and only act upon them, they do not have the toxic side effects that, for example, chemotherapy drugs have which unfortunately attack both diseased and healthy cells.

The picture shows the initial contact between the ligand and the epidermal growth factor receptor on a tumour cell surface.  The inhibition of EGFR signalling has become a significant target in the fight against cancer.

Iressa, the drug which Astra Zeneca have developed and are currently trialling, acts upon the epidermal growth factor receptor (EGRF) found on many types of cancer cells.  It is taken by mouth.  It acts by blocking the signalling pathways implicated in the proliferation and survival of cancer cells.

In small scale trials Iressa has been shown to have positive effects for many, but not all, patients.  All patients in the early trials had solid malignant tumours known to express EGFR.  These include non small cell lung cancer, ovarian, breast, colorectal, prostate and head and neck tumour types.  The majority of patients taking part in trials had previously failed chemotherapy.  These early trials encourage the belief that Iressa will have application for many cancers.

In the earlier stages of the research process, trials were also carried out in mice using strains of human cancer cells.  The diagram shows the results of these tests in the case of prostate cancer.  The control curve shows the almost inevitable progression to death in untreated mice.  The other curves show the improvement found with a conventional chemotherapy drug and with a combination of this drug and Iressa.

Iressa is now being evaluated in two multi-centre, multinational phase III trials.  Both trials are randomised, parallel group, double blind, placebo controlled studies involving more than 1000 chemotherapy-naïve patients with advanced non small cell lung cancer.  The primary objective of these studies, which should lead to publishable results next year, is to show that Iressa improves overall survival when compared to placebo.  Secondary end points include improvements in disease related symptoms and quality of life.

The Prostate Research Campaign UK will publish further information as it becomes available.