An in-depth look at the latest research conducted at the Center for Genomic Science of IIT in Milan
On December 19, 2024, data from the AIOM report on cancer in Italy were presented in Rome. The report confirmed breast cancer as the most prevalent oncological condition among women, affecting 925,406 individuals and accountable for nearly half (45%) of all women living after a cancer diagnosis. Still in 2024, the International Agency for Research on Cancer (IARC) identified breast cancer as the most frequently diagnosed cancer in women and the fourth leading cause of death worldwide. These findings highlight the importance of scientific research, screening, and prevention activities in reducing the impact of this disease. At IIT, breast cancer research is primarily conducted at the Center for Genomics Science (CGS) in Milan, also supported by funding from the AIRC Foundation.
In recent months, the CGS research team published three distinct studies in the high-impact journal Nature Communications. These studies shed light on specific genetic characteristics of triple-negative breast cancer— a type of cancer that does not respond to treatments effective against other forms of breast cancer and accounts for about 20% of cases—and on mechanisms common to other equally aggressive cancers.
The team led by Francesco Nicassio, coordinator of IIT’s Milan Center, developed a “genetic barcode” system combined with single-cell genetic sequencing to study the evolution of breast cells and identify those initiating tumor and metastasis formation . Then, the team analyzed the molecular features of these tracked cells, focusing on their genetic, epigenetic, and transcriptional properties. The results revealed that epigenetic factors—modifications that influence gene expression without altering the DNA or RNA sequence—play a key role in both the early development of tumors and metastasis formation. These factors act as a particular molecular signature, referred to by researchers as a “pro-metastatic epigenome,” present in the primary tumor and capable of identifying the most aggressive cells. These findings pave the way for more targeted and effective therapies against this type of cancer.
A different study, led by researcher Stefano Campaner, focused on the ability of cancer cells to replicate their genome rapidly and frequently without errors that would lead to their death. A defining trait of cancer cells is their capacity to transcribe DNA while it is being duplicated. Campaner’s team identified a crucial protein, CDK12, that coordinates DNA duplication and RNA transcription. Furthermore, the researchers discovered that silencing CDK12 (or inhibiting its activity with drugs) triggers a self-destructive mechanism in the tumor cell’s genome, leading to cell death. The discovery highlights potential strategies for developing future targeted therapies that are both effective and selective for cancer treatment.
In a third study, the research group led by Mattia Pelizzola at IIT Milan and at the Department of Biotechnology and Biosciences of the University of Milano-Bicocca developed an innovative technique to analyze cellular transcriptional programs in detail and employed this method to characterize a model of triple-negative breast cancer. Specifically, the team created a tool acting like a magnifying glass called Nanodynamo, which allows researchers to virtually enter cells and track RNA molecules encoded by each gene as they move from the nucleus to the cytoplasm. By leveraging nanopore sequencing technology, Nanodynamo quantifies RNA molecules in various cellular compartments and integrates this data with the number of transcripts produced over the preceding 20 minutes. This technique enables precise observation of the RNA molecules’ life cycle in their various stages of maturation and migration within the cell. When applied to the triple-negative breast cancer model, Nanodynamo revealed previously unattainable details about the transcriptional alterations typical of this cancer and how these changes respond to pharmacological treatments.
