A new class of molecular factors capable of inactivating tumor genes: it is the new therapeutic approach for the treatment of brain tumors, in particular glioblastoma multiforme (GBM) and its relapses developed by a group of researchers from the Irccs Ospedale San Raffaele and the Institute of Neuroscience of the National Research Council of Milan (Cnr-In). The results have just been published in the scientific journal Science Advances.
New anticancer factors
By studying some cancer cells and cancer stem cells in culture, the researchers – coordinated by Vania Broccoli and Alessandro Sessa – have developed new anticancer factors capable of inactivating and silencing particular pro-tumor factors. This action occurs specifically and exclusively in brain tumor cells, thus preventing tumor growth and the onset of relapses. The treatment has proven to be as effective in cancer cells as it is inert – and therefore safe – in healthy ones, such as neurons.
Relapses in glioblastoma multiforme
Glioblastoma multiforme is a very aggressive form of brain tumor that is still difficult to cure, also due to the numerous relapses. Affected patients usually undergo surgery to remove the tumor, followed by radio and chemotherapy. Despite this, it is difficult to prevent tumor recurrence in almost all cases. This is because the few cancer cells left dormant in healthy tissue after the therapies are able to develop resistance to the treatments. “With the aim of achieving long-lasting remission for this type of cancer, for years we have been engaged in the laboratory in the development of an effective strategy to target both residual diseased cells and cancer stem cells, and suppress their tumor activity. “, he claims Vania Broccoli, Head of the Stem Cells and Neurogenesis Unit of the San Raffaele Hospital and of the Cnr-In.
The new therapeutic approach
The research, carried out in vitro and in vivo in experimental models of glioblastoma and was supported by the AIRC Foundation for Cancer Research and the Ministry of University and Research (MUR), paves the way for the development of new potential therapies for this and other types of cancer. Cancer stem cells, often quiescent but able to self-renew and reform the tumor, use particular proteins called ‘transcription factors’ to grow and proliferate. Among these, the SOX2 protein is produced from an oncogene present in most brain tumors, of which it promotes development and aggression. In the laboratory, the researchers blocked the oncogenic activity of SOX2, creating a faithful copy of it but with the opposite function and therefore capable of inhibiting all its target genes.
The genetic avatar that deactivates tumor factors
Thus, this genetic ‘avatar’ is capable of deactivating the entire genetic network downstream of the SOX2 oncogene. “Our idea was to inactivate the SOX2 oncogene, which normally supports tumor malignancy, by creating an antithetical copy, thus developing a real anti-tumor factor”, he says. Alessandro Sessa, researcher of the Stem Cells and Neurogenesis laboratory of the IRCCS San Raffaele Hospital. “To do this, we used a gene therapy technique by inserting the new antitumor factor, called SES (SOX2 Epigenetic Silencer). We were thus able to eliminate or drastically reduce tumor growth in GBM models both in vitro and in vivo. The treatment proved effective and specific for cancer cells and cancer stem cells. We have also been able to ascertain its safety since it does not damage other healthy cells present in the brain tissue, such as neurons or glia ”.
Future applications also for other types of tumors
The results obtained will now have to be confirmed in further laboratory studies before they can be evaluated in clinical trials with patients. “We hope that this new approach will soon complement current therapies for glioblastoma multiforme. The treatment could be carried out at the same time as the surgical removal, without the need to suspend chemo and radiotherapy, now the standard for this type of cancer ”, concludes Vania Broccoli. The results of this study could also be applied to the treatment of other types of cancer. SOX2 is, in fact, present in various types of cancer and in some liver metastases. Furthermore, the developed technique is modular and versatile and could be used, in principle, to convey other anticancer factors, with applications against lung, breast, liver or kidney tumors.