Danish Cancer Institute

📰 NEWS: Research from the Danish Cancer Institute has revealed a vital role for the E3 ligase Pellino 3 (PELI3) in regulating autophagy, a process by which cells recycle nutrients during periods of stress.   This study highlights how PELI3 supports liver health by maintaining lipid balance and preventing harmful fat accumulation, particularly during nutrient deprivation.   This new insight into the mechanisms of autophagy also provides important information for diseases such as cancer, where cellular stress responses play a critical role.   Group leader Lisa Frankel and her team are continuing their research into PELI3, investigating a critical role for this protein and its influence on cancer progression in the near future. In this video Lisa Frankel explains more 👇

What a brilliant way to start 2025! 🌟 🚀   We’re delighted to share that a groundbreaking research initiative led by the Danish Cancer Institute's Professor Jiri Bartek has been awarded an impressive 30 million kr. grant from the Lundbeckfonden / Lundbeck Foundation's Collaborative Projects programme. This funding will drive vital research into the role of Human Cytomegalovirus (HCMV) in brain cancer, with a particular focus on glioblastoma.   Glioblastoma, the most common and aggressive form of brain cancer, remains a challenge in oncology due to the lack of effective treatments. The research team aims to uncover how HCMV— a DNA virus that latently infects most of the global population and is frequently detected in brain tumours — might contribute to the onset and progression of this devastating disease.   The project will explore how HCMV variant viruses disrupt brain cell metabolism, cause genetic instability, and promote tumour growth. The goal is to uncover vulnerabilities in glioblastoma cells.   Professor Bartek explains:    💬 “We are thrilled and deeply grateful for this opportunity to explore HCMV’s role in glioblastoma pathogenesis. By understanding these mechanisms, we hope to uncover new therapeutic avenues to combat this malignant disease.”   This ambitious project is a collaboration between leading scientists from the DCI, the Karolinska Institutet in Stockholm and the University of Turku in Finland, led by Professor Cecilia Soderberg-Naucler.

Drug resistance is one of the biggest challenges in treating melanoma, leaving many patients without effective solutions. Researchers at the Danish Cancer Institute are at the forefront of research that has the potential to transform melanoma treatment. A new project will focus on understanding how the activation of the protein FAK1 contributes to drug resistance in melanoma. Team leader of the Melanoma Research Team at the DCI, Daniela De Zio, explains why this research is so critical: "Drug resistance is one of the biggest challenges in treating melanoma, leaving many patients without effective solutions. By understanding the role of FAK1 in resistance, we can tackle a key problem that prevents therapies from working, opening the door to better and longer-lasting treatment strategies." This research, funded by the Novo Nordisk Foundation, aims to identify biomarkers that can predict patient responses to FAK1 inhibitors and guide the development of more effective, targeted therapies. "By identifying predictive biomarkers to guide the use of FAK1 inhibitors, we aim to offer a lifeline to patients with resistant tumors. This approach can lead to more personalised, effective therapies, reduce treatment failures, and ultimately improve survival and quality of life for melanoma patients," Daniela de Zio says.

📢 New publication:  Researchers from the Genome Integrity research group at the Danish Cancer Institute has just published an article in Nature Cell Biology. The work is done in collaboration with international colleagues, and the results show how alterations in six genes, including FAT1, result in defective homologous recombination (HR) repair of DNA damage among non-small cell lung cancer, one of the leading causes of death in both men and women. In particular, loss of FAT1 caused severe chromosomal instability and whole-genome doubling, i.e. features that lead to tumour progression and resistance to therapy.    In the video below you can hear professor and research group leader, Jiri Bartek, explain the exciting results 👇   The new results are published here (link in comments): Lu WT. et al.: TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling. Nat Cell Biol. 2024 Dec 30. DOI: 10.1038/s41556-024-01558-w. Online ahead of print.

🌟 Introducing the Genome Integrity Group 🌟    Led by Professor Jiri Bartek this group focuses on various mechanistic aspects of the DDR and DNA repair pathways. Their work aims to improve the understanding of cancer development and identify vulnerabilities in cancer cells.   Scroll through the pictures below to learn more about the GIG group and their research work 👇

⭐ Into the unknown: Groth and van Oudenaarden laboratories receive Novo Nordisk Foundation Synergy Grant for Epigenome Fidelity   How reliably are patterns or markers on DNA (that don’t change the genetic code itself) passed from a one cell to its daughter cells? The Groth lab at the Danish Cancer Institute and CPR, University of Copenhagen (Leonie Kollenstart and Anja Groth) and the van Oudenaarden lab at the Hubrecht Institute in the Netherlands (Jeroen van den Berg and Alexander van Oudenaarden) have been awarded a Novo Nordisk Foundation Synergy Grant of DKK 15 million (approximately 2 million EUR) to answer this question. Both teams will use this grant to develop and apply novel technology to study the robustness of copying non-genetic information known as the epigenome. A better understanding of these processes can open new strategies to prevent diseases like cancer and combat ageing.  In this project, the researchers will develop new technologies to study epigenome inheritance on individual DNA molecules as well as single cells. Together with computational models, they aim to determine the fidelity of epigenome inheritance and identify hotspots for epigenome alterations. This knowledge will be applied in models of cancer, tissue regeneration and rejuvenation to understand how epigenomes evolve or mutate across human lifespan. Congratulations to all the researchers on this amazing news. On the picture is seen: Above: scEdU-seq for two cellular models (in cyan and purple) showing distinct replication timing profiles. Below: Researchers from the Groth Lab: Anja Groth and Leonie Kollenstart and the Hubrecht Institute: Alexander van Oudenaarden and Jeroen van den Berg.

⭐ Scientific Achievements in 2024 ⭐ 🔟 This year, The Cancer Structural Biology (CSB) team achieved a major breakthrough with the first use of a novel structure-based protocol linking genetic variant pathogenicity to cellular mechanisms. This approach focused on lysosomal acid sphingomyelinase (ASM), a crucial enzyme in lipid metabolism linked to genetic disorders and cancer. By integrating molecular dynamics simulations with pathogenicity predictions, the team developed a structural atlas of over 400 ASM variants, validated through experiments on 100+ cases. These findings advance our understanding of ASM-related diseases and open the door to therapies such as enzyme replacement therapy. The article “𝑨𝑺𝑴 𝒗𝒂𝒓𝒊𝒂𝒏𝒕𝒔 𝒊𝒏 𝒕𝒉𝒆 𝒔𝒑𝒐𝒕𝒍𝒊𝒈𝒉𝒕: 𝑨 𝒔𝒕𝒓𝒖𝒄𝒕𝒖𝒓𝒆-𝒃𝒂𝒔𝒆𝒅 𝒂𝒕𝒍𝒂𝒔 𝒇𝒐𝒓 𝒖𝒏𝒓𝒂𝒗𝒆𝒍𝒊𝒏𝒈 𝒑𝒂𝒕𝒉𝒐𝒈𝒆𝒏𝒊𝒄 𝒎𝒆𝒄𝒉𝒂𝒏𝒊𝒔𝒎𝒔 𝒊𝒏 𝒍𝒚𝒔𝒐𝒔𝒐𝒎𝒂𝒍 𝒂𝒄𝒊𝒅 𝒔𝒑𝒉𝒊𝒏𝒈𝒐𝒎𝒚𝒆𝒍𝒊𝒏𝒂𝒔𝒆” was published in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease in October 2024.

⭐ Scientific Achievements in 2024 ⭐ 9️⃣ In September, scientists from the Danish Cancer Institute published groundbreaking findings that unveiled new insights into the behaviour of RAD51, a key DNA repair protein, in Bloom Syndrome (BS). The findings not only provide a deeper understanding of the mechanisms behind the genomic instability observed in Bloom Syndrome but also offer critical lessons about the fundamental processes leading to cancer. Group leader in the Nucleolar Stress and Disease group, Dorthe Helena Larsen, stressed the importance of the findings: “This is important for the way we think about causes of genome instability, one of the leading mechanisms in cancer development. Our study shows that instability in the ribosomal DNA can impact the genome broadly, and it will therefore be important to further understand how changes in the ribosomal DNA promote cancer development.”

⭐ Scientific Achievements in 2024 ⭐ 8️⃣ Another key scientific achievement of 2024 was a study published in The Lancet Oncology that provides reassuring news for postmenopausal women undergoing treatment for early breast cancer. The study demonstrated that women treated with aromatase inhibitors—a common hormone therapy used to prevent breast cancer recurrence—did not face an increased risk of major adverse cardiovascular events, such as heart attacks or ischemic strokes, compared to those who did not receive the treatment. Mads Melbye, Director of Research at the Danish Cancer Institute and a co-author of the study, described the findings as excellent news for women receiving this therapy. “These findings are important and reassure both patients and clinical staff that aromatase inhibitors can be used without compromising the patient’s heart health,” he said. 𝑰𝒔𝒄𝒉𝒂𝒆𝒎𝒊𝒄 𝒄𝒂𝒓𝒅𝒊𝒐𝒕𝒐𝒙𝒊𝒄𝒊𝒕𝒚 𝒐𝒇 𝒂𝒓𝒐𝒎𝒂𝒕𝒂𝒔𝒆 𝒊𝒏𝒉𝒊𝒃𝒊𝒕𝒐𝒓𝒔 𝒊𝒏 𝒑𝒐𝒔𝒕𝒎𝒆𝒏𝒐𝒑𝒂𝒖𝒔𝒂𝒍 𝒑𝒂𝒕𝒊𝒆𝒏𝒕𝒔 𝒘𝒊𝒕𝒉 𝒆𝒂𝒓𝒍𝒚 𝒃𝒓𝒆𝒂𝒔𝒕 𝒄𝒂𝒏𝒄𝒆𝒓 𝒊𝒏 𝑫𝒆𝒏𝒎𝒂𝒓𝒌: 𝒂 𝒄𝒐𝒉𝒐𝒓𝒕 𝒔𝒕𝒖𝒅𝒚 𝒐𝒇 𝒓𝒆𝒂𝒍-𝒘𝒐𝒓𝒍𝒅 𝒅𝒂𝒕𝒂 was published in November 2024

⭐ Scientific Achievements in 2024 ⭐ 7️⃣ The next scientific achievement of 2024 that we are highlighting next is how scientists from the Danish Cancer Institute have implemented machine-learning and AI-based techniques to identify and compare protein structures in greater detail. In this video, first author and senior scientist Kenneth Schou explains how computational biology is driving new discoveries in unprecedented ways. All data, scripts, input files, and output files are open-source and can be found in the article that has just been published in 𝑵𝒂𝒕𝒖𝒓𝒆 𝑪𝒐𝒎𝒎𝒖𝒏𝒊𝒄𝒂𝒕𝒊𝒐𝒏𝒔. Reference: 𝑺𝒄𝒉𝒐𝒖 𝑲𝑩. 𝒆𝒕 𝒂𝒍.: 𝑬𝒙𝒑𝒍𝒐𝒓𝒊𝒏𝒈 𝒕𝒉𝒆 𝒔𝒕𝒓𝒖𝒄𝒕𝒖𝒓𝒂𝒍 𝒍𝒂𝒏𝒅𝒔𝒄𝒂𝒑𝒆 𝒐𝒇 𝑫𝑵𝑨 𝒎𝒂𝒊𝒏𝒕𝒆𝒏𝒂𝒏𝒄𝒆 𝒑𝒓𝒐𝒕𝒆𝒊𝒏𝒔. 𝑵𝒂𝒕𝒖𝒓𝒆 𝑪𝒐𝒎𝒎𝒖𝒏𝒊𝒄𝒂𝒕𝒊𝒐𝒏𝒔 𝒗𝒐𝒍𝒖𝒎𝒆 15, 𝑨𝒓𝒕𝒊𝒄𝒍𝒆 𝒏𝒖𝒎𝒃𝒆𝒓: 7748 (2024)