trabectedin + olaparib

Trabectedin + olaparib is an investigational combination therapy being studied primarily for the treatment of advanced or metastatic sarcomas and breast cancer. Trabectedin is a DNA minor groove binder and alkylating agent that disrupts cell division by binding to the minor groove of DNA and interfering with transcription-coupled nucleotide excision repair pathways. It also blocks cell cycle progression at the G2 phase and inhibits overexpression of multidrug resistance genes[5]. Olaparib is a small molecule inhibitor of poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair; it induces synthetic lethality in tumor cells with defective homologous recombination repair mechanisms[1][4]. The combination has shown synergistic antitumor activity in preclinical models by inducing double-stranded DNA breaks, G2/M arrest, apoptosis, and deregulation of the DNA damage response machinery[2][3][6]. This synergy appears independent of BRCA1 status. Clinical trials are ongoing to evaluate efficacy in patients with unresectable or metastatic sarcoma[8].

Other names

ET-743ET743ET 743MK-7339MK7339MK 7339AZD2281AZD-2281AZD 2281