Program
The research unit of Cancer Genome Dynamics is focused on developing new tools to study chromothripsis and cancer genome evolution. We are particularly interested in how catastrophic processes, like chromothripsis, can shape the evolution of the cancer genome during the different steps of tumorigenesis.
Our research plan is based on three main pillars:
- Developing tools to faithfully recapitulate cancer initiation and progression;
- Chromothripsis in pediatric and adult cancers;
- Identifying vulnerabilities of ecDNA-positive tumors.
The research unit of Cancer Genome Dynamics is focused on developing new tools to study chromothripsis and cancer genome evolution. We are particularly interested in how catastrophic processes, like chromothripsis, can shape the evolution of the cancer genome during the different steps of tumorigenesis.
The development of models to faithfully recapitulate human diseases, particularly cancer, has provided the ground for a better understanding of the mechanisms regulating tumor initiation and progression. Remarkably, this knowledge has led to the discovery of novel therapeutic approaches that have revolutionized the way we treat -no more- deadly tumors. The more the model mimics the disease, the easier it will be to identify successful treatment.
Our lab is focused on developing the next-generation cancer models that more faithfully recapitulate the genomic complexity observed in patients. These preclinical systems will provide a foundation for identifying novel vulnerabilities in cancer cells and for testing therapeutic strategies that specifically target the complexity of the cancer genome.
We are particularly interested in catastrophic events able to reshape the genomic landscape of cancer cells. Among these, chromothripsis is a chromosomal shattering process in which a chromosome undergoes multiple simultaneous rearrangements.
Due to its catastrophic nature, chromothripsis is a major contributor to the formation of complex ecDNA and ecDNA heterogeneity, and it has also been suggested as a mechanism driving drug resistance and tumor evolution by accelerating genomic DNA amplifications.
The generation of preclinical tumor models driven by chromothripsis and its functional byproducts, complex ecDNA, provides a unique platform to assess ecDNA vulnerabilities and identify more effective therapeutic treatments. Particularly relevant for cancer patients is the full identification of key players involved in the maintenance and dynamics of these chromosomal aberrations, thus providing a strong rationale for the design of novel therapeutic strategies.