Cancer Invasion and Resistance
The aim of our research is to understand cancer-induced molecular changes, especially those that regulate lysosomal activity and function leading to enhanced invasion and metastasis, in order to find novel ways to target these often still untreatable, malignant functions of cancer.
Our research
At CIR we employ innovative strategies to combat drug resistance and to inhibit the invasive potential of cancer cells, focusing on aggressive, treatment-resistant breast and ovarian cancers. We are particularly interested on the influence of cancer-induced lysosomal activity and cholesterol in these processes.
Our current efforts center on developing personalized treatments for platinum-taxane-resistant ovarian cancer and for understanding the role of HER2 signaling and lysosomes in standard treatment resistant breast cancer. To mimic the complexity of real tumors, we employ 3D cultures, including tumor organoids from ovarian cancer patients and spheroids from breast and ovarian cancer cells. Our cutting-edge approach integrates 3D confocal high-throughput microscopy, advanced image analysis, RNA interference, CRISPR-Cas9, and lentiviral plasmid delivery techniques to uncover new insights and therapeutic possibilities.
Analysis of tumor organoids
Ki67
Pax8
Pax8
Emma 3
In our research, we culture tumor organoids using high-grade serous ovarian cancer (HGSC) patient-derived tumor tissue, creating stable 3D tissue cultures resembling the original tumors to study them in laboratory conditions. These cultures serve as valuable tools for translational and pre-clinical investigations, enabling us to gain insights into drug resistance mechanism, tumor growth and invasion and allow us to explore innovative personalized medicine approaches.
Selected publications:
Lauridsen AR, Skorda A, Winther NI, Bay ML, Kallunki T: Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers. J Exp Clin Cancer Res 2024; 43(1):254
Skorda A, Lauridsen AR, Wu C, Huang J, Mrackova M, Jank V, Sztupinski Z, Strauss R, Bilgin M, Maeda K, Liu B, Luo Y, Jäättelä M, Kallunki T: Activation of invasion by oncogenic reprogramming of cholesterol metabolism via increased NPC1 expression and macropinocytosis. Oncogene 2023; 42:2495–2506
Lahtinen A, Lavikka K, Virtanen A, Li Y, Jamalzadeh S, Skorda A, Lauridsen AR, Zhang K, Marchi G, Isoviita VM, Ariotta V, Lehtonen O, Muranen TA, Huhtinen K, Carpén O, Hietanen S, Senkowski W, Kallunki T, Häkkinen A, Hynninen J, Oikkonen J, Hautaniemi S: Evolutionary states and trajectories characterized by distinct pathways stratify ovarian high-grade serous carcinoma patients. Cancer Cell 2023;41(6):1103-1117
Skorda A, Bay ML, Hautaniemi S, Lahtinen A, Kallunki T: Kinase inhibitors in the treatment ovarian cancer: current state and future promises. Cancers 2022: 14(24):6257
Hansen MB, Postol M, Tvingsholm S, Nielsen IØ, Dietrich TN, Puustinen P, Maeda K, Dinant C, Strauss R, Egan D, Jäättelä M, Kallunki T: Identification of lysosome-targeting drugs with anti-inflammatory activity as potential invasion inhibitors of treatment resistant HER2 positive cancers. Cell Oncol 2021: 44(4):805-820
Group leader: Tuula Kallunki
Tuula Kallunki received her PhD in Biochemistry and Molecular Biology at the University of Oulu, Finland in 1992, and completed her post-doctoral training in the Department of Pharmacology at the UCSD, USA after which she moved to the Danish Cancer Society with a Marie Curie Fellowship.
Besides being a group leader in DCI, she is currently also affiliated as an Associate Professor to the Department of Drug Design and Pharmacology at the University of Copenhagen, where she is connected to the Personalized Medicine Cluster. In addition to her research activities, Tuula Kallunki has acted as a consultant for biotechnology companies, co-organized several scientific symposia and as an expert evaluator for various international grant agencies. She is currently an editor for two scientific journals and act as a referee for various scientific journals.
ORCID: 0000-0002-8571-383X
Key funding
EU Horizon 2020: DECIDER
Fabrikant Chas. Otzens fond: OVACAN
Købmand Niels Erik Munk Pedersen Fonden: OVACAN
Grosserer Alfred Nielsen og Hustrus Fond
The Danish Cancer Society Scientific Committee
Dansk Kræftforskningsfond