Millions of cancer patient are treated with anthracycline drugs (of which doxorubicin is the best known) annually. Although these anthracycline drugs are quite effective in a number of cancer types, they coincides with severe side effects, especially cardiotoxicity and the induction of therapy-induced tumors. Although these drugs are used in the clinic daily, the exact mechanism is not fully understood. By making chemically modified analogues of these drugs we aim to gain more inside in the mechanism by which these drugs function. Hereby we hope to make an effective but less toxic variant.
These anthracycline drugs are topoisomerase II inhibitors. Blocking the catalytic cycle of the enzyme results in DNA double strands breaks. Our lab showed that there is a second mechanism by which the anthracycline drugs function, namely eviction of histones. This histone eviction mechanism by these drugs contributes largely to the anticancer effect of these compounds, however, how eviction of histones by the drugs leads to cell death is still unclear. Therefore, we are interested in the transcriptional- and epigenomic changes and the role of the innate immune system in anthracycline induced cell death.
I studied Biomolecular science at the VU University in Amsterdam, the Netherlands. For my masters I performed a research internship at the VU the group of Holger Lill and a second research internship at the Netherlands Cancer Institute, in the group of Jacques Neefjes. After I finished my masters I started my PhD in the group of Jacques Neefjes.
Genome-Wide Identification and Characterization of Novel Factors Conferring Resistance to Topoisomerase II poisons in Cancer.
Ruud H. Wijdeven, Baoxu Pang, Sabina Y. van der Zanden, Xiaohang Qiao, Vincent Blomen, Marlous Hoogstraat, Esther H. Lips, Lennert Janssen, Lodewyk Wessels, Thijn R. Brummelkamp and Jacques Neefjes
Cancer Research, 2015. Doi: 10.1158/0008-5472. CAN-15-0380