The symmetrical inheritance of chromosomes during cell division is essential for the survival of healthy daughter cells. Cancer cells often break this symmetry, resulting in dramatic changes of chromosome number and/or structure. Such changes enable rapid evolution that could lead to increased aggressiveness and to therapy resistance
Chromosome catastrophes can lead to multiple cancer driving events, including deletion of tumor suppressor genes, gene fusions, and gene amplification. We are specifically interested in the role of intra-chromosome amplifications (HSRs) and extra-chromosome DNA (ecDNA) amplifications in cancer formation and progression. We are studying the biology behind ecDNA formation and maintenance, and the effect such amplifications have on cancer cell behavior.
The biggest challenge in cancer therapy is the development of resistance. Our group studies the evolutionary forces that drive therapy resistance formation, in order to identify targetable vulnerabilities. We focus on mechanisms of DNA repair that enable ecDNA amplifications in cancer progression and resistance formation and explore different approaches to target the formation and evolution of ecDNA. Our vision is to develop a combination therapy approach that targets cancer cells survival and in parallel inhibits the evolutionary potential that often leads to resistance formation.
