#Eureka

Basic cancer researchers and cancer patients live in different worlds, that often don’t meet. Through Oncode’s Patient Engagement Program, we want to narrow this gap and facilitate both researchers’ and patients’ understanding of each other’s world. In the video we prepared for World Cancer Day, Inge Reus and Niels Heine (both participants in the Patient Engagement Programme) and Oncode Investigator Peter ten Dijke (LUMC) explain the value of the collaboration between (former) patients and researchers.

Read more and watch the video here:

Meeting up each November for a deep dive into important scientific topics at the Royal Tropical Institute (KIT) has been a tradition for many years. Despite the challenges, we made it happen this time too. With a variety of topics presented by a great mix of experts, and lots of energy and joy that came from simply getting together again like in the good old times before the corona pandemic, we look back at a two-day successful hybrid meeting.

Read the highlights here.

Following a brainstorm session in 2021, looking for ideas for cross-disciplinary synergies that can tackle difficult challenges in cancer research, an exciting new idea came out. Cancer immunotherapy is a game-changing treatment, but its success revealed a major obstacle: the resistance of tumors to this T-cell mediated therapy. Marking the launch of the Oncode Accelerator Project, a group of Oncode Investigators are now joining forces to face this problem, by calling in the help of other immune cells, the so called ‘innate leukocytes’.

Read more about this here.

Since our last digital magazine landed in your digital mailbox last October, Oncode researchers have published over 150 scientific articles. For this issue of our digital magazine, we handpicked two highlight papers in different areas: unwanted side effects of CRISPR-Cas9 genome editing and a new avenue for treating AML.

Oncode Investigators René Medema, Elzo De Wit and Wilbert Zwart teamed up to dive into an unwanted side effect of CRISPR-Cas9 mediated genome editing. This technology has brought a novel alternative to induce endogenous double-strand breaks (DSBs) at desired genomic locations. This system therefore allows for the study of the DNA damage response and its consequences. To achieve efficient gene editing, the CRISPR/Cas9 system needs to be delivered in an accurate manner. These delivery systems can be either viral or non-viral. The work of Medema, De wit and Zwart shows that delivery through lentiviral vectors has an unwanted effect. These vectors can integrate into the endogenous genomic target location which leads to unintended activation of a target gene. Good to know for the scientific field, especially since there are alternative nonintegrative systems, such as synthetic gRNAs delivered in the form of RNA complexes. This manuscript titled 'Unexpected gene activation following CRISPR-Cas9-mediated genome editing' was published in EMBO Reports.

Ruud Delwel and his team recently published new work into new treatment opportunities for acute myeloid leukemia (AML). Their work elucidates how the oncogene EVI1 employs an oncogenic mechanism of hijacking of hematopoietic super-enhancers for its overexpression in EVI1 positive AMLs. This is a typical example of how novel fundamental knowledge can lead to new ideas for treatment. Knowing what drives aberrant oncogene expression is an important step in understanding how to tackle this with therapeutic strategies. To further investigate this new line of work, the team developed novel in vitro models to investigate the regulation and interfere with hijacking of super-enhancers. This research was published in Nature Communications with the title 'The leukemic oncogene EVI1 hijacks a MYC super-enhancer by CTCF-facilitated loops'.

These are just two of many great studies coming out of the different Oncode laboratories. Every two months we collect 4-5 new impactful papers from our labs and share the essence and impact of those studies in a newsletter. If you are interested to stay on top of what we do, reach out to our communications team, and we will add you to our mailing list.

In November 2021, Oncode Institute and many partners submitted the Oncode-PACT Growth Fund proposal. Its goal? Bring together and build out the state-of-the-art drug development infrastructure, make it easily accessible and innovate the drug development process itself. By building early validation and de-risking into the drug development pipeline, our approach should result in higher chances of success. The proposal has passed the final review by the Netherlands Enterprise Agency (RvO), and it will now be reviewed by the Growth Fund Committee. The advice of the Growth Fund Committee and the cabinet’s decision are expected at the beginning of April.

You can read more about the Oncode-PACT Growth Fund proposal here.