TUMOR, RNA IS EXPANDING THE HORIZONS OF PRECISION MEDICINE

In cancer research, RNA is stealing the show from DNA. In fact, today only 20% of cancer patients benefit from drugs capable of targeting the DNA mutation that causes cancer.

The other large portion of patients requires new therapeutic approaches. In this sense, RNA is assuming a central role, thanks to its important involvement in the mechanisms of carcinogenesis. At the Istituto Nazionale Tumori Regina Elena IRCCS (IRE) a translational research group of non-coding RNAs is active: “We are committed to identifying micro-RNAs for diagnostic and therapeutic use – explains Giovanni Blandino Head of the team, and of the IRE Translational Oncological Research Unit – to identify biomarkers associated with prognosis and response to therapies, and RNA-based molecular signatures. Thanks to our studies, we have already filed several patents, obtaining important funding for research.”

At the 5th workshop on translational oncology underway at IRE, international experts discuss the most innovative results of the latest RNA studies.

“For the future – declares Gennaro Ciliberto, IRE Scientific Director and expert molecular biologist –we expect the diagnostic and therapeutic use of RNAs to be the cornerstone of precision and personalized medicine. We are already verifying this with mRNA vaccines, a great success of technology against both infectious diseases and tumors. For the latter, the goal is to design a specific mRNA therapeutic vaccine for each patient, after having sequenced the tumor cells and identified the mutated proteins in the context of the neoplasm. ”With mRNA technology we go even beyond vaccination, the method has in fact the ability to make the cells of our body produce therapeutic proteins such as monoclonal antibodies. The potential of the technology is enormous due to the number of targeted therapies that can be implemented.

The translational research team of the Regina Elena Institute focuses research on non-coding RNAs, i.e. those that do not produce proteins and which, at the level of the DNA from which they originate, represent around 70% of the human genome. For many years this RNA was considered junk. Today we know that they have a central role in regulating gene expression mechanisms. A mutation of the non-coding RNA modifies the genetic information: it turns on the wrong light bulbs or activates them in the wrong way, producing proteins or altered cells such as cancer cells.

At the IRE, on the occasion of the international workshop, young researchers are presenting their research on the new world of diagnostic and therapeutic RNAs. Some examples:

“We have identified – explains Luigi Fattore, researcher at the SAFU IRE laboratory – specific non-coding micro-RNAs, which play an important role in resistance to therapy against metastatic melanoma. Furthermore, microRNAs can also be delivered into cancer cells via lipid nanoparticles, in order to counteract the phenomenon of resistance.”

“Even in triple-negative breast cancers – continues Roberto Dinami, researcher at the IRE Translational Oncology Research Unit – it has been demonstrated that lipid vesicles containing certain microRNAs, and “launched” against neoplastic cells, inhibit the telomeric protein TRF2, responsible for tumor progression.

“In patients with recurrence or distant metastases for head and neck cancer, who no longer benefit from previous therapies, we have identified – concludes Claudio Pulito, of the Oncological Translational Research Unit – unconventional mediators of response to chemotherapy treatment. Small pieces of RNA that block the activity of fundamental proteins whose role is to arrest tumor growth. The next goal will be to identify new strategies to inhibit these micro-RNAs or bypass their activity. We plan to expand the study going to characterize additional mechanisms of resistance to standard treatments such as chemo and radiotherapy.”