Pantelidou Constantia, Jadhav Heta, Kothari Aditi, Liu Renyan, Wulf Gerburg M, Guerriero Jennifer L, Shapiro Geoffrey I
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Bayer Pharmaceuticals, Cambridge, MA, USA.
NPJ Breast Cancer. 2022 Sep 6;8(1):102. doi: 10.1038/s41523-022-00471-5.
Poly (ADP-ribose) polymerase (PARP) inhibitors exert their efficacy via synthetic lethal effects and by inducing cGAS/STING-mediated immune responses. We demonstrate that compared to monotherapies, combined PARP inhibition and STING agonism results in increased STING pathway activation, greater cytotoxic T-cell recruitment and enhanced dendritic cell activation in BRCA1-deficient breast cancer models. The combination markedly improved anti-tumor efficacy in vivo, with evidence of complete tumor clearance, prolongation of survival and induction of immunologic memory.
聚（ADP - 核糖）聚合酶（PARP）抑制剂通过合成致死效应和诱导cGAS/STING介导的免疫反应发挥其疗效。我们证明，与单一疗法相比，联合PARP抑制和STING激动作用在BRCA1缺陷型乳腺癌模型中可导致STING通路激活增加、细胞毒性T细胞募集增加以及树突状细胞激活增强。该联合疗法在体内显著提高了抗肿瘤疗效，有肿瘤完全清除、生存期延长和免疫记忆诱导的证据。
