Stopping Breast Cancer in Its Tracks
Breast cancer is a constantly evolving disease. Successive genetic mutations and alterations, often over a prolonged period of time, cause some breast cancers to grow beyond control, invade surrounding tissues and disseminate through the body. This spreading to other tissues and organs (metastasis) is responsible for virtually all deaths in breast cancer. It is well recognized that cancer cells are more prone to further changes in their genetic information than normal cells—a feature known as genomic instability. Genomic instability can drive cancer metastasis and resistance to therapies. Accordingly, increased genomic instability is associated with more negative clinical outcomes such as reduced disease-free survival. The cause for increased genomic instability in cancer cells remains incompletely understood. Defects in the repair and maintenance of genetic information, housed in the cell nucleus, are thought to play crucial roles.
Jan Lammerding, Biomedical Engineering, and his lab are investigating a novel paradigm for genomic instability in cancer cells with the potential to improve and expand the use of existing drugs, as well as develop new drugs specifically targeting newly identified susceptibilities in cancer cells that may prevent metastatic disease.
The Lammerding lab believes that temporary mechanical disruption of the nucleus during cancer cell migration through tight spaces can induce genomic instability in breast cancer and contribute to cancer progression and metastasis. As cancer cells invade surrounding tissues and make their way to distant metastatic sites, the cells, and particularly their nucleus, must undergo severe deformations to squeeze through microscopic spaces between other cells and within dense tissues.
The Lammerding team has developed advanced experimental tools to detect nuclear disruption in living cells and tissues. Applying these techniques to a panel of different breast cancer cells and healthy controls, they assess the effect of transient nuclear rupture on genomic instability; investigate whether the susceptibility to nuclear damage correlates with the aggressiveness or metastatic potential of cancer cells; determine how cells manage to overcome repetitive nuclear rupture.
Since nuclear disruption could also result from increased pressure inside the tumor, such approaches may even reduce tumor growth before metastasis occurs. The goal of the Lammerding lab is to revolutionize treatment regimens with safe and effective interventions.