Investing in (new) technologies and facilities - which are available to all Oncode researchers - is one of the ways in which Oncode contributes to breakthroughs in cancer research. The Oncode drug screening centres of expertise at the LUMC and the NKI are examples of such facilities. They provide Oncode researchers with advice and support to perform complex compound screens with the Drug Repurposing library. Oncode Investigator Ruud Delwel explains how he currently works with the drug screening center at the NKI.
The goal of Oncode Institute is to translate the results of ground-breaking fundamental research into the clinic faster, in order to improve the chances of cancer patients. Investing in (new) technologies and facilities - which are available to all Oncode researchers - is one of the ways in which Oncode contributes to breakthroughs in cancer research.
The Oncode drug screening centres of expertise at the LUMC and the NKI are examples of such facilities. They provide Oncode researchers with advice and support to perform complex compound screens with the Drug Repurposing library. Oncode Investigator Ruud Delwel (Erasmus MC) and his group are currently working with the drug screening center at the NKI on an interesting research project.
Ruud explains: “Our research group is highly focused on molecular defects driving the development of acute myeloid leukemia (AML). AML is a rare, but highly fatal form of leukemia, which affects mostly elderly people. When you look at AML cells under a microscope, they all look alike. But patients with AML can respond very differently to treatment: There are individuals that respond well to treatment. There’s a group that doesn’t respond to the treatment at all. Unfortunately, the biggest group of patients respond well to treatment at first, but the cancer comes back after a few years and then the outlook for those patients is very poor.”
“Biologically and molecularly, AML is not one disease. Different subtypes with distinct abnormalities can be distinguished based on different genetic defects. For many years, the focus of our group has been on one of the most aggressive forms of AML, i.e. AML with overexpression of the EVI1 oncogene. This gene is overexpressed as the result of chromosomal translocations involving the locus where EVI1 resides (chromosome 3q26). We previously uncovered the mechanism of EVI1 overexpression: EVI1 hijacks so-called super enhancers from other genes that upon translocation hyperactivate the expression of this oncogene in AML cells. In two recent papers, we further uncovered the aberrant function of the hijacked enhancers driving EVI1 oncogene expression.”
“We now generated two reporter assays that I believe can be of importance to find the regulators of aberrant transcription and uncover drugs able to interfere with oncogene overexpression. We therefore contacted Jacqueline Staring to explore the possibilities of performing a compound screen, which we eventually executed at the NKI Robotics and Screening Center.”
“We carried out the first drug screen using our EVI1-reporter models with the ~6.000 compounds of the Oncode Drug Repurposing library, after which we performed a secondary dose response series with ~100 compounds that looked promising in the initial screen. Based on this data we have identified several compounds that have an effect on EV1. We will now focus our efforts on understanding the mechanisms behind the action of these compounds. We are very excited to have found several molecules that have an effect on a previously undruggable oncogene, something that may hold great promise on the future treatment of this subgroup of AML patients and hopefully beyond this group. Our cooperation with the facility runs very smoothly, and we are especially happy with the help of Roderick Beijersbergen, who is leading this facility, and his experienced team.”
All Oncode facilities can be found via https://www.oncode.nl/facilities. Researchers who want a full overview of the possibilities with regards to technologies, facilities, infrastructures, and online platforms are encouraged to login at the Oncode Community Platform*, where all information is available. Alternatively, they can contact Jacqueline Staring, Programme Manager at Oncode Institute, directly. More information about the added value of the Oncode technologies and facilities are discussed by Jacqueline in this interview.
*All Oncode researchers have access to the Oncode Community Platform, if you have troubles logging in, please contact [email protected] and don’t hesitate to update your own personal community platform page