Cancer and Medicine

The research group Cancer and Medicine is under formation. Three teams are so far established in the group: Translational Cancer Genomics, Treatment and Cancer, and Melanoma Research Team

Translational Cancer Genomics

DNA repair pathway aberrations are an integral part of cancer development but they are absent in normal cells, and thus they constitute as an important therapeutically targetable feature of human cancer. Small molecules that specifically kill DNA repair deficient cells offer significant clinical benefit for, for example, ovarian cancer patients that are treated with PARP inhibitors (niraparib, olaparib). The success of such therapy, however, depends on the presence of specific DNA repair pathway aberrations in a given cancer case. Our group has developed several next-generation sequencing based methods to achieve this, with some of those reaching the clinical application stage (myChoice HRD assay).

We are also actively searching for agents that can provide PARP inhibitor-like therapeutic benefit in cancer cases with a different DNA repair pathway aberration. We recently developed a diagnostic method to identify nucleotide excision repair deficient cancer cases that will likely benefit from the experimental cancer therapy agent, irofulven. We plan to initiate clinical trials based on this agent in collaboration with the Rigshospitalet.

Cancer immunology has provided major breakthroughs in the treatment of advanced, metastatic cancer. However, we have only limited understanding of the mechanism of action of immunology based therapy and we do not understand why only certain patients respond. ln collaboration with Herlev Hospital (Center for Cancer lmmune Therapy) we are combining next generation sequencing based approaches with translational oncology research to improve the efficacy oi cancer immunotherapy.

Börcsök J, Diossy M, Sztupinszki Z, Prosz A, Tisza V, Spisak S, Rusz O, Stormoen DR, Pappot H, Csabai I, Brunak S, Mouw KW, Szallasi Z: Detection of Molecular Signatures of Homologous Recombination Deficiency in Bladder Cancer. Clin Cancer Res 2021; online ahead of print

Diossy M, Sztupinszki Z, Krzystanek M, Borcsok J, Eklund AC, Csabai I, Pedersen AG, Szallasi Z: Strand Orientation Bias Detector to determine the probability of FFPE sequencing artifacts. Brief Bioinform 2021; online ahead of print

Börcsök J, Sztupinszki Z, Bekele R, Gao SP, Diossy M, Samant AS, Dillon KM, Tisza V, Spisák S, Rusz O, Csabai I, Pappot H, Frazier ZJ, Konieczkowski DJ, Liu D, Vasani N, Rodrigues JA, Solit DB, H Hoffman-Censits JH, Plimack ER, Rosenberg JE, Lazaro J-B, Taplin M-E, Iyer G, Brunak S, Lozsa R, Van Allen EM, Szüts D, Mouw KW, Szallasi Z: Identification of a Synthetic Lethal Relationship between Nucleotide Excision Repair Deficiency and Irofulven Sensitivity in Urothelial Cancer. Clin Cancer Res 2021; 27(7):2011-2022

Sztupinszki Z, Diossy M, Krzystanek M, Borcsok J, Pomerantz MM, Tisza V, Spisak S, Rusz O, Csabai I, Freedman ML, Szallasi V: Detection of Molecular Signatures of Homologous Recombination Deficiency in Prostate Cancer with or without BRCA1/2 Mutations. Clin Cancer Res 2020; 26(11):2673-2680

Poti A, Berta K, Xiao Y, Pipek O, Klus GT, Ried T, Csabai I, Wilcoxen K, Mikule K, Szallasi Z, Szuts D: Long-term treatment with the PARP inhibitor niraparib does not increase the mutation load in cell line models and tumour xenografts. Br J Cancer 2018;119(11):1392-1400

Team Leader: Zoltan Szallasi

Portrait photo of team leader, professor Zoltan Szallasi

ORCID: 0000-0001-5395-7509

TCG Staff

Contact information for all staff in TCG

Key Funding

Novo Nordisk Foundation

Independent Research Fund Denmark

Velux Foundation

Danish Cancer Society Scientific Committee

Treatment and Cancer

The team Treatment and Cancer uses high-quality Danish and Nordic registry data as basis for their research.

We use nationwide registry data to investigate safety, risks and benefits of drugs in relation to cancer and other outcomes. Current drug candidates include (among others) female hormones, antidiabetic drugs, aspirin and other NSAIDs, and drug exposure in early pregnancy.

Ongoing projects include safety studies of drug use in women and in children after drug exposure in pregnancy. We are also interested in potential carcinogenic effects of drug use, and possibilities of repurposing of drugs with potential anti-cancer effects, whether in cancer prevention or as beneficial effects on cancer prognosis.

Skriver C, Friis S, Knudsen LB, Catarig AM, Clark AJ, Dehlendorff C, Mørch LS: Potential preventive properties of GLP-1 receptor agonists against prostate cancer: a nationwide cohort study. Diabetologia 2023;66(11):2007-2016

Pourhadi N, Meaidi A, Friis S, Torp-Pedersen C, Mørch LS: Central nervous system tumours among users of vaginal oestradiol tablets: A nationwide population-based study. Eur J Neurol 2023;30(9):2811-2820

Meaidi A, Torp-Pedersen C, Lidegaard Ø, Mørch LS: Ectopic Pregnancy Risk in Users of Levonorgestrel-Releasing Intrauterine Systems With 52, 19.5, and 13.5 mg of Hormone. JAMA 2023;329(11):935-937

Mørch LS, Gamborg M, Hemmingsen CH, Skovlund CW, Kjær SK, Hargreave M: In Utero Exposure to Hormonal Contraception and Mortality in Offspring with and without Cancer: A Nationwide Cohort Study. Cancers 2023;15(12):3163

Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø: Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med 2017;377(23):2228-2239

Team Leader: Lina Steinrud Mørch

PhD, Msc in Public Health, Lina Mørch, is leader for the ‘Treatment and Cancer' group. Lina has taken a special interest in conducting large-scale pharmacoepidemiological studies by use of nationwide prescription and disease registers. Linas main interests are cancer-, reproductive- and pharmacoepidemiology, and she has focused particularly on the influence of postmenopausal hormone therapy and hormonal contraceptives on risk of various health outcomes; including cancer risk.

Lina has worked at Danish (National Institute of Health, Copenhagen University Hospital, and Danish Cancer Institute) and international research institutions (University of California Los Angeles and Medical School of Valencia) during her PhD and postdoc periods. These were followed by a position as Senior Researcher at the Copenhagen University Hospital. In 2017-19, Lina held a position at Novo Nordisk as Senior Epidemiologist working with non-interventional post marketing/Phase IV studies.

ORCID: 0000-0001-6506-2569

TAC Staff

Contact information for all staff in TAC

Key Funding

Danish Cancer Society Scientific Committee

Nordic Cancer Union (NCU)

Novo Nordisk A/S

Sundhedsdonationer

Melanoma Research Team

The Melanoma Research Team drives translational research aimed at uncovering new and more effective therapies for melanoma. By integrating cell and molecular biology with advanced preclinical models, we investigate how melanoma develops, adapts, and resists therapy.

Our work focuses on investigating the molecular mechanisms driving melanoma progression and therapy resistance — both to targeted treatments and immunotherapies. We use genetically engineered mouse models (GEMMs), GEMM-derived allografts, and artificial skin systems to closely mimic the natural course of the disease in the lab. A core part of our research is understanding the heterogeneity and plasticity of melanoma cells and how they interact with their surrounding tumor microenvironment. By doing so, we aim to identify new drug candidates and therapeutic targets.

Illustration of the use of murine melanoma model

We are particularly interested in improving the effectiveness of immune checkpoint inhibitors, especially in so-called "cold" tumors — those with limited immune cell infiltration. Our goal is to develop combination therapies that can help turn these unresponsive tumors into ones that respond to immunotherapy.

We closely collaborate with Rigshospitalet (Department of Oncology and Pediatrics) and Herlev Hospital (Center for Cancer Immune Therapy) as well as with the University of Copenhagen (Department of Immunology and Microbiology) and the University of Southern Denmark (Institute of Molecular Medicine and Department of Biochemistry & Molecular Biology).

Nazerai L, Tsiavou C, Vardouli L, Schmiegelow K, De Zio D. Thiopurine therapy enhances immune checkpoint inhibitor efficacy in low-mutational burden melanoma: A promising anticancer approach. Proc Natl Acad Sci U S A. 2025 Mar 4;122(9):e2423246122

Di Leo L, Pagliuca C, Kishk A, Rizza S, Tsiavou C, Pecorari C, Dahl C, Pacheco MP, Tholstrup R, Brewer JR, Berico P, Hernando E, Cecconi F, Ballotti R, Bertolotto C, Filomeni G, Gjerstorff MF, Sauter T, Lovat P, Guldberg P, De Zio D. AMBRA1 levels predict resistance to MAPK inhibitors in melanoma. Proc Natl Acad Sci U S A. 2024 Jun 18;121(25):e2400566121.

Frias A, Di Leo L, Antoranz A, Nazerai L, Carretta M, Bodemeyer V, Pagliuca C, Dahl C, Claps G, Mandelli GE, Andhari MD, Pacheco MP, Sauter T, Robert C, Guldberg P, Madsen DH, Cecconi F, Bosisio FM, De Zio D. Ambra1 modulates the tumor immune microenvironment and response to PD-1 blockade in melanoma. J Immunother Cancer. 2023 Mar;11(3):e006389

Nazerai L, Willis SC, Yankilevich P, Di Leo L, Bosisio FM, Frias A, Bertolotto C, Nersting J, Thastrup M, Buus S, Thomsen AR, Nielsen M, Rohrberg KS, Schmiegelow K, De Zio D: Thiopurine 6TG treatment increases tumor immunogenicity and response to immune checkpoint blockade. Oncoimmunology 2023;12:2158610

Di Leo L, Bodemeyer V, Bosiso FM, Claps G, Carretta M, Rizza S, Faienza F, Frias A, Khan S, Bordi M, Pacheco MP, Di Martino J, Bravo-Cordero JJ, Daniel CJ, Sears RC, Donia M, Madsen DH, Guldberg P, Filomeni G, Sauter T, Robert C,  De Zio D*, Cecconi F*: Loss of Ambra1 promotes melanoma growth and invasion. Nat Commun 2021; May 5. * Co-last authors

Team leader: Daniela De Zio

Daniela De Zio is the head of the Melanoma Research Team, with a strong background in molecular oncology and mouse genetics. After she obtained her PhD in Molecular and Cellular Biology at the University of Rome Tor Vergata (Italy), she conducted post-doctoral research in different institutes in Italy and Denmark. Her research at DCI is dedicated to unraveling the mechanisms that drive melanoma development, progression and therapy resistance. She is also actively involved in the discovery of novel therapeutic strategies to enhance the efficacy of immune checkpoint inhibitors in cancer treatment.

In 2019, she received the prestigious Melanoma Research Alliance Young Investigator Award to investigate the role of AMBRA1 as a tumor suppressor in melanoma. Since 2023, she is Associate Professor in basal and translational cancer research at the Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark (SDU).

ORCID: 0000-0002-9454-402X