gemcitabine + lurbinectedin

Gemcitabine + lurbinectedin is a combination chemotherapy regimen that demonstrates synergistic antitumor effects through complementary mechanisms of action. **Mechanism of Action:** - **Lurbinectedin**: A synthetic alkaloid that covalently binds to DNA minor grooves, forming adducts that generate double-strand DNA breaks, disrupting DNA-protein interactions and RNA transcription. It also selectively depletes tumor-associated macrophages (TAMs), which leads to cytidine deaminase downregulation in tumors. - **Gemcitabine**: A nucleoside analog that is phosphorylated intracellularly to active metabolites that inhibit DNA synthesis by competing with deoxycytidine triphosphate for incorporation into DNA, leading to chain termination and apoptotic cell death. The combination produces enhanced DNA damage, cell cycle blockage, increased apoptosis, and improved efficacy through lurbinectedin's ability to deplete TAMs, which is particularly relevant in tumors with high macrophage infiltration. The recommended dose is lurbinectedin 3.0 mg flat dose (or 1.6 mg/m²) with gemcitabine 800 mg/m² administered on days 1 and 8 every 3 weeks.

Other names

lurbinectedin + gemcitabine combination