lurbinectedin + doxorubicin

Lurbinectedin + doxorubicin is an investigational intravenous combination therapy under clinical evaluation primarily in *metastatic leiomyosarcoma* (LMS), *soft tissue sarcoma* (STS), and *relapsed small-cell lung cancer* (SCLC)[1][2][3][4][5][6][7]. Lurbinectedin is a synthetic tetrahydroisoquinoline analog that binds to DNA, inhibiting active transcription by causing stalling and degradation of elongating RNA polymerase II, which results in DNA breaks and apoptosis. It also induces selective apoptosis in mononuclear phagocytes and inhibits inflammatory cytokine production[1][2]. Doxorubicin is a cytotoxic anthracycline that intercalates DNA, inhibits topoisomerase II, and causes DNA strand breaks, leading to apoptosis. The combination exploits partially non-overlapping toxicity profiles and has shown synergistic antitumor activity preclinically and in early-phase clinical trials, with encouraging response rates and manageable toxicity in trials involving SCLC and LMS[1][2][5][7].