selinexor + olaparib

Selinexor + olaparib is an investigational oral combination therapy consisting of two small molecule agents with distinct but potentially synergistic mechanisms of action. Selinexor is a selective inhibitor of nuclear export (SINE) that targets exportin 1 (XPO1/CRM1), leading to nuclear retention and reactivation of tumor suppressor proteins and downregulation of oncogenic drivers. Olaparib is a poly(ADP-ribose) polymerase (PARP) inhibitor that impairs DNA repair by inhibiting PARP1 and PARP2, resulting in accumulation of DNA damage especially in cells deficient in homologous recombination repair such as those with BRCA mutations. Preclinical studies have demonstrated that this combination exhibits synergistic anti-tumor activity across multiple cancer models including ovarian cancer and triple-negative breast cancer regardless of BRCA mutation status, likely through enhanced disruption of DNA damage response pathways and increased apoptosis. The combination is currently being evaluated in clinical trials for advanced cancers such as small cell lung cancer[1][2][3][4][8].

Brand names

none known for the combination; individual drugs are marketed as Xpovio (selinexor) and Lynparza (olaparib)