Lectures and seminars Guest seminar - Prof. Gergely Szakács
Thursday, February 12 at 1pm in room Nils Ringertz, Biomedicum. Title: “Targeting adaptive mechanisms to tackle multidrug resistance in cancer".
Welcome to guest seminar by Prof. Gergely Szakács
Professor Gergely Szakács has made pioneering contributions to understanding multidrug resistance (MDR) in cancer. His work established the concept of collateral sensitivity, reframing MDR transporters from obstacles to exploitable vulnerabilities and shaping thousands of subsequent studies. Based on over a decade of study of MDR mechanisms, Professor Szakács’s recent work identifies a novel chemotherapeutic strategy showing outstanding efficacy.
Time: 13:00-14:00, February 12
Place: Nils Ringertz, Biomedicum
Title: “Targeting adaptive mechanisms to tackle multidrug resistance in cancer”.
Abstract
Therapy resistance has long been attributed to the selection of pre-existing resistant clones or the acquisition of mutations during chemotherapy. Increasingly, however, resistance is recognized as a dynamic and adaptive process rather than the sole consequence of stable genetic alterations. Using in vitro systems and genetically engineered mouse models of triple-negative breast cancer, we identify drug-tolerant persister (DTP) cells that emerge in response to chemotherapy. Single-cell RNA sequencing reveals that adaptive programs—including senescence-associated pathways characterized by cell cycle arrest, epithelial-to-mesenchymal transition (EMT), and reversible upregulation of multidrug resistance mechanisms such as the efflux transporter P-glycoprotein—are transiently induced during treatment. Importantly, the DTP state is reversible, as cells can resume proliferation and give rise to populations resembling the original drug-naïve cells. However, recovery from this state can be prevented by targeting key adaptive pathways engaged in persister cells. Our findings highlight adaptive plasticity as a central driver of multidrug resistance and suggest that therapeutic strategies aimed at eliminating or disabling transient adaptive states may prevent or delay the emergence of durable therapy resistance.
Recent publications
Safe delivery of a highly toxic anthracycline derivative through liposomal nanoformulation achieves complete cancer regression.
Füredi A, Tóth S, Hegedüs K, Szabó PT, Gaál A, Barta G, Naszályi LN, Kiss K, Bölcskei K, Szeltner Z, Bajtai E, Gombos B, Kiss D, Cserepes MT, Kiss A, Pokreisz P, Kenner L, Högler S, Magyar C, Cowles JD, Csiszar A, Tóvári J, Szüts D, Helyes Z, Varga Z, Mező G, Szakács G
Mol Cancer 2025 Oct;24(1):269
Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cells.
Szebényi K, Füredi A, Bajtai E, Sama SN, Csiszar A, Gombos B, Szabó P, Grusch M, Szakács G
Drug Resist Updat 2023 Nov;71():101007
Unshielding Multidrug Resistant Cancer through Selective Iron Depletion of P-Glycoprotein-Expressing Cells.
Cserepes M, Türk D, Tóth S, Pape VFS, Gaál A, Gera M, Szabó JE, Kucsma N, Várady G, Vértessy BG, Streli C, Szabó PT, Tovari J, Szoboszlai N, Szakács G
Cancer Res 2020 Feb;80(4):663-674