Anticancer therapies often become ineffective due to the emergence of multidrug resistance (MDR). Mechanisms ensuring survival of cancer cells include the inactivation or efflux of drug molecules, increased DNA repair, avoiding apoptosis, reducing target protein expression, suspending cell cycle, and bypassing immunosurveillance. Current estimations suggest that drug resistance and the resulting ineffectiveness of the drug treatment are responsible for up to 90% of the cancer related deaths.
The Drug Resistance Research Group is aiming to understand and target mechanisms of cancer drug resistance, by establishing new in vitro and in vivo models and by developing novel compounds and treatment strategies to target crucial cancer cell populations which drive relapse after therapy.
Projects
Identification and characterization of Multidrug resistant- or MDR-selective compounds
Development of LiPyDau, an extremely potent anticancer agent targeting therapy resistant tumors
Investigating the mechanisms of cisplatin resistance in triple negative breast cancer
Improving current chemotherapy protocols by personalization with algorithm-assisted therapy design
Developing a point-of-care microfluidic device for Therapeutic Drug Monitoring in cancer treatment
Studying the role of drug tolerant persisters in therapy resistance and relapse
Szebényi*, A. Füredi*, E. Bajtai, S.N. Sama, A. Csiszar, B. Gombos, P. Szabó, M. Grusch, G. Szakács, Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cells, Drug Resist. Updat. 71 (2023) 101007. https://doi.org/10.1016/j.drup.2023.101007.
L. Kovács, T. Ferenci, B. Gombos, A. Füredi, I. Rudas, G. Szakács, D.A. Drexler, Positive Impulsive Control of Tumor Therapy—A Cyber-Medical Approach, IEEE Trans. Syst. Man Cybern. Syst. (2023) 1–12. https://doi.org/10.1109/TSMC.2023.3315637.
Z. Gyöngy, G. Mocsár, É. Hegedűs, T. Stockner, Z. Ritter, L. Homolya, A. Schamberger, T.I. Orbán, J. Remenyik, G. Szakacs, K. Goda, Nucleotide binding is the critical regulator of ABCG2 conformational transitions, eLife 12 (2023) e83976. https://doi.org/10.7554/eLife.83976.
V.F.S. Pape, R. Palkó, S. Tóth, M.J. Szabó, J. Sessler, G. Dormán, É.A. Enyedy, T. Soós, I. Szatmári, G. Szakács, Structure–Activity Relationships of 8-Hydroxyquinoline-Derived Mannich Bases with Tertiary Amines Targeting Multidrug-Resistant Cancer, J. Med. Chem. 65 (2022) 7729–7745. https://doi.org/10.1021/acs.jmedchem.2c00076.
E. Karai, K. Szebényi, T. Windt, S. Fehér, E. Szendi, V. Dékay, P. Vajdovich, G. Szakács*, A. Füredi*, Celecoxib Prevents Doxorubicin-Induced Multidrug Resistance in Canine and Mouse Lymphoma Cell Lines, Cancers 12 (2020) 1117. https://doi.org/10.3390/cancers12051117.
M. Cserepes*, D. Türk*, S. Tóth, V.F.S. Pape, A. Gaál, M. Gera, J.E. Szabó, N. Kucsma, G. Várady, B.G. Vértessy, C. Streli, P.T. Szabó, J. Tovari, N. Szoboszlai, G. Szakács, Unshielding Multidrug Resistant Cancer through Selective Iron Depletion of P-Glycoprotein–Expressing Cells, Cancer Res. 80 (2020) 663–674. https://doi.org/10.1158/0008-5472.CAN-19-1407.
L. Hámori, G. Kudlik, K. Szebényi, N. Kucsma, B. Szeder, Á. Póti, F. Uher, G. Várady, D. Szüts, J. Tóvári, A. Füredi*, G. Szakács*, Establishment and Characterization of a Brca1−/−, p53−/− Mouse Mammary Tumor Cell Line, Int. J. Mol. Sci. 21 (2020) 1185. https://doi.org/10.3390/ijms21041185.
P. Kannan*, A. Füredi*, S. Dizdarevic, T. Wanek, S. Mairinger, J. Collins, T. Falls, R.M. van Dam, D. Maheshwari, J.T. Lee, G. Szakács, O. Langer, In vivo characterization of [18F]AVT-011 as a radiotracer for PET imaging of multidrug resistance, Eur. J. Nucl. Med. Mol. Imaging 47 (2020) 2026–2035. https://doi.org/10.1007/s00259-019-04589-w.
Z. Rakvács, N. Kucsma, M. Gera, B. Igriczi, K. Kiss, J. Barna, D. Kovács, T. Vellai, L. Bencs, J.M. Reisecker, N. Szoboszlai, G. Szakács, The human ABCB6 protein is the functional homologue of HMT-1 proteins mediating cadmium detoxification, Cell. Mol. Life Sci. (2019). https://doi.org/10.1007/s00018-019-03105-5.
T. Windt, S. Tóth, I. Patik, J. Sessler, N. Kucsma, Á. Szepesi, B. Zdrazil, C. Özvegy-Laczka, G. Szakács, Identification of anticancer OATP2B1 substrates by an in vitro triple-fluorescence-based cytotoxicity screen, Arch. Toxicol. 93 (2019) 953–964. https://doi.org/10.1007/s00204-019-02417-6.
*shared authorship
Collaborations
International
University of Bern, Bern (Switzerland)
Investigating drug resistance mechanisms in organoids and animal models
Medical University of Vienna, Vienna (Austria)
Developing novel treatments to eliminate drug tolerant persister cells
Seoul National University, Seoul (Korea)
University of Pennsylvania, Philadelphia (USA)
University of Freiburg, Freiburg (Germany)
National
Microsystem Laboratory, HUN-REN Centre for Energy Research, Budapest (Hungary):
Development of a point-of-care microfluidic device for Therapeutic Drug Monitoring in cancer treatment (POC-TDM), EU funded MSCA project (https://cordis.europa.eu/project/id/101065044)
Department of Experimental Pharmacology, National Institute of Oncology, Budapest (Hungary):
Modelling human cancer in mice, in vivo testing of new drug candidates
Óbuda University, Budapest (Hungary):
Chemotherapy individualization using algorithm-assisted therapy design
University of Szeged, Szeged (Hungary):
Characterization of metal-8-hydroxyquinoline complexes
University of Pécs, Pécs (Hungary):
Development of a novel bioimpedance-based diagnostic tool for early cancer detection
Eötvös Lóránd University, Budapest (Hungary):
Ongoing patent application for an extremely effective liposomal anticancer agent, Monitoring metal ions in cancer cells
Budapest University of Technology and Economics, Budapest (Hungary):
Testing anticancer cinchona alkaloids
R&D Companies
Actome GmbH, Freiburg (Germany)
Investigating of protein-protein and protein-lncRNA interactions in cellular senescence
Clinomics Europe Ltd, Budapest (Hungary)
Identifying circulating tumor cells in blood samples
Creative Cell Ltd., Budapest (Hungary)
Testing radioprotective agents on human cell lines
Collaborations within the Research Centre for Natural Sciences:
Epigenetic and Genome Editing Research Group, Institute of Molecular Life Sciences
Genome Stability Research Group, Institute of Molecular Life Sciences
Metabolic Drug-interactions Research Group, Institute of Molecular Life Sciences
Non-coding Genome Research Group, Institute of Molecular Life Sciences
Chemical Biology Research Group, Institute of Organic Chemistry
Medicinal Chemistry Research Group, Institute of Organic Chemistry
Functional Nanoparticles Research Group, Institute of Materials and Environmental Chemistry
Biological Nanochemistry Research Group, Institute of Materials and Environmental Chemistry