Therapy Escape of Cancer

Prof. Dr. Sven Rottenberg, Direktor
Prof. Dr. Sven Rottenberg, Direktor

Cancer Therapy Resistance

Patients with tumors that are defective in DNA repair by homologous recombination (HR) are often sensitive to DNA-repair targeting agents. However, despite initial responses to cancer therapy, resistance of primary or disseminated tumors eventually emerges, which minimizes therapeutic options and greatly reduces survival. The molecular mechanisms underlying this therapy escape are mostly unclear.

In my group we are studying the basic mechanisms of therapy escape by using distinguished mouse models for BRCA1- or BRCA2-deficient breast cancer, which closely mimic the disease found in humans. Due to the BRCA inactivation, the tumors that arise lack HR-directed DNA repair; an Achilles heel that has provided a therapeutic opportunity to eradicate tumors with DNA damage-causing agents. However, similar to the situation in cancer patients, we observe that cancer cells in these models can escape the deadly effects of classical chemotherapy, novel targeted drugs or radiotherapy. Thus, these resistance models that we have established provide a unique opportunity to explore therapy escape mechanisms