Targeting brain cancer by acting on cancer stem cells thanks to a protein involved in the development of glioblastoma, as well as various other cancers. This is the attack ‘strategy’ identified by a group of researchers from the European Institute of Oncology who demonstrated, in preclinical models, the efficacy of a new treatment against glioblastoma, the deadliest brain tumor. The results of the research, supported by the Airc Foundation and the Ministry of Health, have just been published in the prestigious journal Science Translational Medicine.
Glioblastoma and killer cells
According to the latest Aiom data, 6,300 new cases of malignant tumors of the central nervous system are estimated in Italy, of which 90% represented by gliomas. Glioblastoma constitutes 54% of all gliomas: it can occur at any age, but 70% is diagnosed between 45 and 70 years. Since 2005, the standard of treatment has been the largest and safest possible surgical resection, followed by concomitant chemotherapy and radiotherapy and subsequent maintenance chemotherapy. “Among the various causes that make glioblastoma so lethal – he explains Giuliana Pelicci, director of the Research Unit at the Department of Experimental Oncology and professor of Molecular Biology at the University of Eastern Piedmont who led the research – there is the presence of cancer stem cells, the subpopulation of cells responsible for both resistance to current therapies both of the progression of the disease. We have discovered how to eliminate these killer cells by interfering with their extraordinary ability to adapt and survive ”.
Brain tumors: new hope from the combination of two drugs
by Tina Simoniello
A new approach against glioblastoma
The researchers focused their attention on LSD1, a protein involved in the development of glioblastoma, as well as various other cancers, which plays an active role in the maintenance of stem cells as it promotes their ability to adapt to different stress stimuli, both present in the environment surrounding the tumor, which induced by anti-cancer therapies. “We have shown – continues Pelicci – that pharmacological inhibition of LSD1 activity reduces the ability of cancer stem cells to self-maintain, thus slowing down tumor growth. We have observed this process in preclinical models in which it was possible to recapitulate some types of heterogeneous human glioblastomas from a molecular point of view. We also noticed that the treatment has no effect on normal brain cells. The results therefore confirm that we are faced with a new approach to be tested as soon as possible in the clinic for the treatment of glioblastomas ”.
Direct attack on cancer stem cells
In particular, researchers have identified a new LSD1 inhibitor: the molecule DDP_38003, already known for its therapeutic potential against leukemia. This molecule manages to cross the blood brain barrier, reaches the brain, binds to LSD1 expressed in tumor stem cells and blocks their activity. Without the action of this precious protein, cancer stem cells can no longer resist stress and die. “Our study demonstrates that LSD1 is a key target for molecular therapies against glioblastoma – they continue Stefania Faletti and Daniela Osti, IEO researchers and first authors of the article – and that the inhibitor we studied acts independently of the gene profile of the tumor. This is an important point because glioblastoma is a highly heterogeneous tumor, with different characteristics from patient to patient, and this heterogeneity is one of the main reasons why non-targeted drugs have so far obtained very limited results “. Although much remains to be investigated on LSD1 and its mechanisms of action and interaction with cancer stem cells, the priority now is to activate a clinical trial to investigate the toxicological aspects of its inhibition, in the hope of soon arriving at a more effective treatment for. glioblastoma.
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