Over 5 million patients each year receive chemotherapy with anthracyclines. Although life-saving, these drugs have toxic effects on the heart. Cancer survivors are often affected by irreversible damage in their cardiac cells which may lead to heart failure. Using induced pluripotent stem cells (hiPSC) derived from different individuals, we aim at generating cardiac cells and develop alternative treatments to protect the heart during chemotherapy.
Impact
A maximum cumulative dose of anthracyclines is currently imposed due to cardiotoxic risk, limiting cancer treatment. Moreover, this risk appears to be influenced by patient genetics. The development of drugs killing the tumor without harming the heart would transform the options for patients and the life quality of cancer survivors. Deriving hiPSCs from patients with different genetic susceptibility to heart disease allows to identify broadly effective drugs.
reNEW research
We have generated cardiac cells from hiPSCs of different patients, who did and who did not develop cardiotoxicity after anthracycline treatment, and from patients carrying genetic variants associated with heart disease. We have developed cell viability and functional assays to compare in vitro their susceptibility to the most common anthracycline, doxorubicin, and to newly developed chemical analogs which showed less cardiotoxicity in animal models.
Image description
Stem cell-derived heart muscle cells treated with doxorubicin, showing disrupted structures of the sarcomeres, the contractile units of the heart: alpha-sarcomeric actinin (red), cardiac troponin (green). Nuclei in blue.
Credits
Giulia Campostrini (senior researcher), Bellin/Mummery lab, Anatomy & Embryology, reNEW Leiden, the Netherlands. Image acquired by: Viviana Meraviglia.
