A toxin produced by certain strains of Escherichia coli, such as the one that causes "hamburger disease," induces programmed cell death in astrocytoma, the most common and most deadly primary brain tumour in humans. In the first animal model of the human tumour, researchers from Toronto's Hospital for Sick Children and the University of Toronto achieved complete regression of human tumours growing in mice with just one injection of verotoxin (Oncol Res 1999;11:33-9).
Astrocytomas are "particularly resistant to treatment," explains Dr. Clifford Lingwood. Patients with the most malignant form of astrocytoma, glioblastoma multiforme, survive an average of 12 months. Current treatment consists of surgical debulking of the tumour and radiation therapy.
Now that verotoxin has shown its worth in mice, Lingwood is hoping to test it in humans, pending approval of the research. "The plan is to have a few adult patients staggered with older children. We would be looking at its safety in adults before trying it in children."
During cranial surgery, the neurosurgeon would debulk the tumour and inject verotoxin directly into any residual tumour. The main concern about using verotoxin is that verotoxin-producing E. coli can cause hemolytic uremic syndrome.
"It's an obstacle, but I don't think it's insurmountable," Lingwood says. He points out that the syndrome occurs mainly in young children. "It's quite likely that adults and children older than 3 years are resistant to the toxin." There is also evidence that the bacterial infection itself, not just the toxin it produces, is implicated in hemolytic uremic syndrome. "Verotoxin given alone may be less pathogenic."
There has been a flurry of research into the cancer-killing properties of verotoxin in astrocytoma, Burkitt's lymphoma, ovarian cancer and some other cell lines. The receptor for verotoxin is found in elevated levels in many samples from these forms of cancer, and particularly from drug-resistant tumours.
Verotoxin induces cell death in both the tumour cells (antineoplastic) and the vascular cells around the tumour (antiangiogenic). Thanks to this 2-pronged approach, it appears ideally suited to use as a cancer treatment, the authors conclude.-C.J. Brown, CMAJ