Discovering the role of titin (TTN) in anthracycline-induced cardiotoxicity in breast cancer.

Anthracyclines are the mainstay of chemotherapeutic treatment in a wide range of malignancies, including breast cancer. Cardiotoxicity is a well-known and feared adverse effect of anthracyclin therapy and due to the growing population of cancer survivors, cardiovascular disease in these patients is expected to escalate. Unless we can identify high-risk patients for anthracycline therapy, today's breast cancer patients may become tomorrow 's heart failure patients. However, there is an important inte individual susceptibility for the development of cardiotoxicity and at present, it is not possible to predict which patients will develop cardiotoxicity. It was recently shown that genetic variants in titin, an import anchoring protein in the cardiomyocytes, can cause a predisposition to dilated cardiomyopathies and are also more prevalent in chemotherapy-induced cardiotoxicity. In this research project we investigate if mutations in titin increase the susceptibility for cardiotoxicity to anthracyclines, in order to identify high -risk patients. If this can be confirmed, the impact on both the individual patient (morbidity, mortality) and on society will be huge. The development of an hiPSC-CM model harbouring different TTNtv will allow us to test different possible therapeutic and preventive measures for this high risk population.

Keywords:CARDIOLOGY, CHEMOTHERAPY, BREAST CANCER

Disciplines:Cardiology