Reframing cancer drug resistance: transporters, persister cells, senescence, and emerging therapeutic strategies

Nagy, Péter and Kis, Anna Kamilla and Bajtai, Eszter and Haffaressas, Ines Lidia and Gombos, Balázs and Bereczki, Dóra and Szebényi, Kornélia and Szakács, Gergely and Tóth, Szilárd and Füredi, András (2026) Reframing cancer drug resistance: transporters, persister cells, senescence, and emerging therapeutic strategies. MAGYAR ONKOLÓGIA, 70 (2). pp. 118-127. ISSN 0025-0244

Text f3d9a4e2-1a64-4636-b3de-ef09a0c9860f.tmp - Published Version Download (2MB)

Abstract

Cancer drug resistance remains one of the greatest barriers to durable therapeutic success. Here, we reframe resistance as a dynamic landscape shaped by transporter‑mediated efflux, reversible drug‑tolerant persister states, and therapy‑induced senescence. This review highlights areas where our group has made substantial contributions, with a particular focus on our own experimental and conceptual advances. We show how P‑glycoprotein (P-gp) overexpression, traditionally viewed as an obstacle sustaining cancer multidrug resistance (MDR), creates exploitable metabolic vulnerabilities, enabling the development of MDR‑selective compounds. We demonstrate that persister cells rely on transient P‑gp-mediated detoxification, revealing a therapeutic window during drug‑free intervals. We further show that senescence is not a terminal fate but a relapse‑initiating state requiring targeted intervention. Finally, we illustrate how pharmacokinetics and dosing schedules can be harnessed to reshape tumor evolution, culminating in LiPyDau, a next‑generation liposomal anthracycline with durable activity against resistant tumors. Together, these insights outline a unified strategy for anticipating, intercepting, and ultimately overcoming cancer drug resistance.

Actions (login required)

View Item