Einstein discovery could treat childhood cancer
triggering rare but usually fatal cancers known as rhabdoid
tumours. This discovery could lead to novel therapies for these
tumours that mainly affect children.
Current drug regimens for rhabdoid tumours don't target this molecule, explaining why 80 per cent of diagnosed children die from this type of cancer.
Cyclin D1, the molecule now implicated in rhabdoid tumours, is made by cells and promotes routine cell division-and is greatly overproduced in several types of cancer, including 30 to 40 per cent of human breast cancers.
Yet for most of these cancers, it's not clear whether Cyclin D1 overproduction causes the disease or is merely the consequence of some event during carcinogenesis. The study showed that Cyclin D1 overproduction is essential for causing rhabdoid tumours.
Rhabdoid tumours begin with loss of the tumour suppressor gene INI1. In proving Cyclin D1's involvement, the researchers "knocked out" one of the two INI1 tumour- suppressor genes in mice.
The researchers, from the Albert Einstein College of Medicine, discovered that rhabdoid tumours developed exhibiting marked overproduction of Cyclin D1.
Furthermore, when these tumour-prone mice were mated with mice devoid of Cyclin D1 because both copies of their Cyclin D1 gene had been knocked out, the offspring failed to develop tumours-clear evidence that Cyclin D1 is essential for rhabdoid tumours to form.
A rhabdoid tumour is a rare and highly malignant tumour of childhood, first described in 1978. These tumours were initially considered an aggressive variant of Wilms' tumour of the kidney, however, with newer diagnostic techniques, these tumours are believed to represent a distinct entity.
Since that time, there have been fewer than 50 cases reported, although it is likely that some cases previously identified as medulloblastoma or as primitive neuroectodermal tumors (PNET) are in fact rhabdoid tumours.
These tumours occur in young children, mean age at diagnosis of 3.5 years, with a range of 2 to 13 years. There are no reported cases in adults. Rhabdoid tumours occur equally in males and females. The location can be supratentorial, intraventicular, and infratentorial.
The research is published this week in the Proceedings of the National Academy of Sciences.
