Titia DeLange, PhD

Understanding how cancer cells survive DNA damage to continue growing and resist therapies.

Impact

Despite major advances in breast cancer detection and treatment, many unanswered questions remain about how the disease develops and why it becomes aggressive in some individuals. One critical area of investigation centers on the genetic instability found in most breast tumors, or changes to bundles of DNA called chromosomes that allow cancer cells to grow uncontrollably. Understanding how these changes arise, and how cancer cells survive despite them, may reveal new, more effective treatment strategies.

Dr. de Lange’s research focuses on the role of telomeres which are protective caps at the ends of chromosomes. In normal cells, telomeres prevent DNA damage, maintain genome stability, and limit the number of times a cell can divide. In early-stage breast cancer, telomeres become critically short because of rapid cell division, leading to genome instability. Later in cancer development, cells can restore telomeres allowing cancer cells to survive and multiply. By identifying key vulnerabilities in the way breast cancer cells manage genome instability, her research could lead to novel, targeted therapies.

Progress Thus Far

Dr. de Lange and her team are pursuing two major avenues of research. The first focuses on breast cancer cells with short telomeres. They have found that these cells are especially sensitive to disruption of a protein complex called CST–Polα/primase, which is essential for telomere maintenance. Using advanced gene-editing tools, they have confirmed that even minor disruptions to this complex can severely impact cells with short telomeres, but not those with longer ones. This discovery points to a potential weakness in certain breast cancers—one that could be exploited for new, targeted therapies.

The second line of research investigates a newly discovered process by which cancer cells survive by attaching new telomeres to broken chromosomes. They have built specialized breast cell models to study this phenomenon and its role in helping cells tolerate DNA damage.

What’s next

The team will continue to identify and exploit genomic instabilities and vulnerabilities in breast cancer cells. Early results show that their model systems are working as intended and could shed light on how breast cancer cells overcome key barriers to tumor progression. Understanding these critical mechanisms could lead to a new therapeutic strategy that interferes with telomere formation in cancer and thus, tumor cell survival.