That gene, known as Brg1, is a key regulator of leukemia stem cells that are the root cause of the disease, resistance to treatment and relapse, said researchers at the Institute for Research in Immunology and Cancer (IRIC) of Université de Montréal, Canada. "When we removed the Brg1 gene, the leukemia stem cells were unable to divide, survive and make new tumours. In other words, the cancer was permanently shut down," claimed Julie Lessard, principal investigator and her colleagues at IRIC.
One difficulty with targeting cancer stem cells is that many genes essential for their function are also essential for normal stem cells, and therapies targeting them can end up harming healthy stem cells as well. "Strikingly, the Brg1 gene is dispensable for the function of normal blood stem cells - making it a promising therapeutic target in leukemia treatment," explained Pierre Thibault, principal investigator at IRIC and co-author. "The next step would be to develop a small-molecule inhibitor to successfully block Brg1 function in leukemia, thus demonstrating the clinical relevance of this discovery," noted Guy Sauvageau, principal investigator at IRIC.
The group is now performing experiments to identify such drugs that can disarm the Brg1 gene, thereby stopping leukemia stem cells from generating malignant cells. Cancer stem cells appear to be more resistant to radiotherapy and chemotherapy than the 'bulk' of the tumour and, therefore, are often responsible for cancer relapse.
As such, inhibiting residual leukemia stem cells from dividing is the key to obtain irreversible impairment of tumour growth and long-term remission in patients, said the study reported in the scientific journal Blood.