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Temozolomide + olaparib is an investigational oral combination therapy consisting of two small molecule drugs: temozolomide, an alkylating agent that induces DNA damage, and olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor that impairs DNA repair. The rationale for this combination is to enhance cytotoxicity in cancer cells by both inducing DNA lesions (temozolomide) and inhibiting their repair (olaparib), leading to increased apoptosis. This strategy exploits synthetic lethality, particularly in tumors with defective homologous recombination repair mechanisms such as those with BRCA mutations or "BRCA-like" phenotypes. The combination has shown promising activity in relapsed small-cell lung cancer, advanced uterine leiomyosarcoma, glioblastoma models, and is being explored in Ewing sarcoma and rhabdomyosarcoma[1][2][3][4][5][6].
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