A new approach to treating aggressive prostate cancer: an IRB-IOR patent
Institutional Communication Service
Andrea Cavalli has been a researcher at the Institute for Research in Biomedicine (IRB) since 2012 and has served as the Director of the Computational Structural Biology Laboratory since 2016. His research integrates advanced computational methods, such as molecular dynamics simulations and artificial intelligence techniques, to understand how sequence, structure and dynamics define the function of biomolecules. He particularly focuses on antigen-antibody interactions and the development of new therapeutic strategies. Concetta Guerra obtained her PhD at the IRB in 2020 and currently holds the position of PostDoc researcher in the Computational Structural Biology Laboratory. Her work combines computational and experimental approaches to study post-translational modifications of transcription factors involved in cancer, particularly prostate cancer, and to develop innovative antibody-based therapies.
Recently, in collaboration with Giuseppina Carbone of the Institute for Oncology Research (IOR), they obtained prestigious funding from Innosuisse for their innovative project "An antibody-based strategy targeting activated oncogenic ERG in prostate cancer", which led to the creation of the startup MethylX, supported by the USI Startup Centre.
Andrea Cavalli, Concetta Guerra, what makes your project innovative, and how did you come up with the idea?
"The project stems from the idea of targeting a known player in prostate cancer, the transcription factor ERG, by exploiting a previously unexplored vulnerability. ERG is overexpressed in about 50% of prostate tumours, contributing to several characteristics of malignancy, such as increased cell proliferation and the ability to form metastases.
Despite its clinical relevance, there are currently no targeted therapies against ERG because, like other transcription factors, it lacks structural features that make it easily targeted by traditional drugs. In collaboration with Giuseppina Carbone and Carlo Catapano of the Institute for Oncology Research (IOR), we discovered that methylation of a specific region of ERG further amplifies its oncogenic activity.
At the same time, this modification generates a unique molecular signature, absent in healthy cells, which makes ERG an ideal target for the development of highly selective therapies. Thanks to the integration of Artificial Intelligence (AI), structural bioinformatics and new protein engineering techniques, we have developed a miniaturised antibody capable of selectively recognising methylated ERG and blocking its function. One of the innovative aspects of our project is that the antibody is not administered as a ready-made protein, but rather in the form of DNA encapsulated in nanoparticles, allowing cancer cells to produce it directly within themselves. This combination of new-generation antibodies and gene therapy technologies represents a pioneering strategy for treating a well-defined subgroup of patients with advanced prostate cancer. Furthermore, we are already working to extend this approach to other transcription factors, thereby building a technological platform capable of making oncogenes traditionally considered "untreatable" due to their post-translational modifications "targetable."
Why did you choose to patent your idea?
"We chose to patent this technology to safeguard an innovation that has the potential to make a significant clinical impact and to facilitate its industrial development. Protecting our intellectual property is crucial for attracting investment and forming collaborations with pharmaceutical partners, which will help accelerate the process of translating our discoveries from the laboratory to the clinic. The patent will serve as the foundation for a robust startup focused on transforming this innovation into an effective treatment for patients."
How will your idea improve the diagnosis and treatment of prostate cancer? And how does it differ from current methods?
"Today, advanced prostate cancer is mainly treated with hormone therapy, chemotherapy and drugs targeting known genetic alterations, but there are no strategies that directly target oncogenic transcription factors such as ERG. Our technology introduces a paradigm shift: the antibody we have developed selectively recognises methylated ERG, offering new possibilities for both precision diagnostics, allowing for accurate identification and stratification of patients, and for targeted therapy. Instead of administering pre-produced antibodies, we use therapeutic DNA delivered in nanoparticles, so that cancer cells produce it directly within themselves. This approach increases efficacy and specificity, reduces side effects and makes administration easier and less invasive for the patient. This strategy also serves as a platform: the combination of AI, protein engineering, and gene therapies can be extended to other oncogenes previously considered "untreatable", opening up new perspectives in precision medicine.
What was the path that led you from scientific discovery to patent, and what are the next steps in bringing this technology to patients?
"Our journey began with the discovery, in collaboration with Giuseppina Carbone and Carlo Catapano of the IOR, that ERG methylation is a hallmark of the most aggressive prostate tumours. This result prompted us to design targeted antibodies using advanced artificial intelligence and structural modelling tools, which were then validated experimentally. When preliminary data confirmed the therapeutic potential, we spoke with USI Transfer and the idea for the startup MethylX was born to accelerate its development. We are currently optimising the DNA- and nanoparticle-based gene delivery system to complete preclinical studies and establish industrial partnerships to support clinical development. Our goal is to transform this academic discovery into a precision therapy that can tangibly improve patient prognosis.
